Nonspecific Hyperresponsiveness Research Articles

Folliculitis might be associated with pathergy-positivity in patients with Behçet syndrome.

Pathergy test indicates nonspecific hyper-reactivity of the skin to aseptic trauma in Behçet syndrome (BS) and is considered as an adjunctive diagnostic test with a good specificity albeit with low sensitivity. We tested the hypothesis that a relationship exists between active clinical manifestations of BS and the pathergy-positivity when performed simultaneously. Pathergy test and detailed dermatologic examination were done in 105 BS patients (60M/45F); who were seen consecutively at the multi-disciplinary BS outpatient clinic in a single tertiary center. Information regarding demographic and clinical characteristics, pathergy test results at diagnosis, and details about treatment were obtained from patient charts. Disease activity was assessed using Behçet Disease Current Activity Form. Among 105 patients, 27 (25.7%) were pathergy-positive at the time of the study visit whereas 40.9% were pathergy-positive at the time of the diagnosis. There was no relation between pathergy test and patient age or disease duration, either. Pathergy-positivity was significantly more common in patients with folliculitis compared to those without folliculitis (40.7% vs 19.2%; P = .026). The test was also positive in all 3 patients with leg ulcers due to venous stasis. We found that among all skin-mucosa lesions only the presence of folliculitis was associated with pathergy positivity with statistical significance. It was also remarkable that the current pathergy was positive in all 3 patients with active leg ulcers but this finding warrants further studies because of the low patient numbers.

Perivascular Innervation in the Nasal Mucosa and Clinical Findings in Patients with Allergic Rhinitis and Idiopathic Rhinitis.

Introduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis. Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR). Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate. Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score. Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.

Trained immunity as a potential target for therapeutic immunomodulation in Duchenne muscular dystrophy.

Dysregulated inflammation involving innate immune cells, particularly of the monocyte/macrophage lineage, is a key contributor to the pathogenesis of Duchenne muscular dystrophy (DMD). Trained immunity is an evolutionarily ancient protective mechanism against infection, in which epigenetic and metabolic alterations confer non-specific hyperresponsiveness of innate immune cells to various stimuli. Recent work in an animal model of DMD (mdx mice) has shown that macrophages exhibit cardinal features of trained immunity, including the presence of innate immune system "memory". The latter is reflected by epigenetic changes and durable transmissibility of the trained phenotype to healthy non-dystrophic mice by bone marrow transplantation. Mechanistically, it is suggested that a Toll-like receptor (TLR) 4-regulated, memory-like capacity of innate immunity is induced at the level of the bone marrow by factors released from the damaged muscles, leading to exaggerated upregulation of both pro- and anti-inflammatory genes. Here we propose a conceptual framework for the involvement of trained immunity in DMD pathogenesis and its potential to serve as a new therapeutic target.

Macrophage plasticity in Duchenne muscular dystrophy: a nexus of pathological remodelling with therapeutic implications.

Duchenne muscular dystrophy (DMD) is characterized by chronic skeletal muscle necrosis, leading to muscle regeneration failure and fibrosis. Although macrophages (MPs) are normally essential for muscle regeneration, dysregulated MP function promotes pathological muscle remodelling. Infiltrating MPs can be predominantly pro-inflammatory (M1 biased), anti-inflammatory (M2 biased) or of a mixed phenotype and can originate from the adult bone marrow (monocyte dependent) or embryonic precursors (monocyte independent). In mdx mice (genetic model of DMD) lacking either Toll-like receptor (Tlr) 2 or Tlr4, it is found that MP infiltration of dystrophic muscle is significantly reduced and that the MP phenotype is shifted toward a more anti-inflammatory profile. This is accompanied by significant improvements in muscle histology and force production. Lack of the chemokine receptor CCR2, which impedes monocyte release from the bone marrow, leads to similar beneficial effects in mdx mice. Evidence was also found for Tlr4-regulated induction of trained innate immunity in MPs cultured from the bone marrow of mdx mice before their entry into the muscle. These MPs exhibit epigenetic and metabolic alterations, accompanied by non-specific hyper-responsiveness to multiple stimuli, which is manifested by potentiated upregulation of both pro- and anti-inflammatory genes. In summary, exaggerated recruitment of monocyte-derived MPs and signs of trained innate immunity at the level of the bone marrow are features of the immunophenotype associated with dystrophic muscle disease. These phenomena are regulated by Toll-like receptors that bind endogenous damage-associated molecular pattern (DAMP) molecules, suggesting that DAMP release from dystrophic muscles modulates MP plasticity at the bone marrow level through Toll-like receptor-driven mechanisms.

Chronic rhinitis in children is not a local problem

Allergic rhinitis is the most common pathology among all allergic diseases. The article presents the epidemiologic and pathogenetic issues of the allergic rhinitis. The underdiagnosis of allergic rhinitis and its underestimation as a systemic pathology were observed in various countries. The importance of allergic rhinitis in paediatric practice, its impact on the quality of life, studies, and cognitive abilities is considered. The extranasal manifestations of the disease, as well as the role of allergic rhinitis in the development of increased respiratory viral morbidity are assessed. The differences between allergic and vasomotor rhinitis (non-allergic non-infectious rhinopathy) are analysed. Frequent interdependence and interaction of the allergic and vasomotor rhinitis are stressed. The signs of nonspecific hyperreactivity of the upper respiratory tract affected by the allergic rhinitis are presented. The role and importance of decongestants in the treatment of both allergic and vasomotor rhinitis are discussed in detail. Vasoconstrictors would help reduce hyperemia and nasal mucosa oedema, reduce the level of mucus secretion, improve the drainage of paranasal sinuses, normalizing the pressure in them. The use of a combination drug – a sympathomimetic combined with a local antihistamine agent would be the most appropriate treatment for patients with AR. The use of intranasal combination therapy for allergic rhinitis is justified: a sympathomimetic phenylephrine combined with a blocker of H1-histamine receptors dimethindene. The insights into the safety and efficacy of above drug combination in paediatric practice are presented. The use of a combination intranasal drug based on phenylephrine and dimethindene in patients with allergic rhinitis is justified in paediatric practice as both symptomatic and pathogenetic treatment. It is also advisable to administer it to treat acute respiratory viral diseases, in the post-viral period with situational exacerbations of the vasomotor component.

Molecular allergodiagnostics capabilities in determining the indications for allergen-specific immunotherapy with house dust mites allergen and its effectiveness in atopic dermatitis patients

BACKGROUND:Atopic dermatitis (AD) is a widespread chronic inflammatory skin disease, in the development of which complex genetic and immune mechanisms, environmental factors, allergens, are involved. An effective method of treating IgE-mediated allergic diseases is allergen-specific immunotherapy (ASIT), which affects all pathogenetically significant links of the allergic process. It is known that as a result of ASIT tissue sensitivity to an allergen, nonspecific tissue hyperreactivity and the intensity of allergic inflammation decrease, which testifies to the rearrangement of the cellular response from Th2 to Th1 with a corresponding change in the cytokine profile. Currently, dozens of scientific papers on the efficacy and safety of subcutaneous and sublingual ASIT in AD have been published; however, the question of the advisability of its appointment still remains unresolved.
 AIM:To investigate the ASIT with house dust mite (HDM) allergens efficacy in AD patients, considering the results of molecular allergy diagnosis.
 MATERIALS AND METHODS:The study was conducted as a prospective comparative open study, including 32 patients with AD (20 children and 12 adults), 90.6% were diagnosed with concomitant respiratory allergic diseases. Molecular allergodiagnostics was performed using microchip technology with purified natural or recombinant allergen components immobilized in the solid phase (Immuno-Solid phase Allergen Chip, ISAC) to quantify allergen-specific IgE (asIgE) against 112 allergen molecules from 51 allergen sources in one study (ImmunoCAP ISAC (Thermofisher, Phadia, Uppsala, Sweden). Patients were divided into two groups depending on the profile of molecular sensitization: with the presence or absence of asIgE to the major allergens ofD. farinaeand/orD. pteronyssinusDer p 1 (p 2) and/or Der f 1 (f 2). All patients passed three consecutive courses of subcutaneous ASIT with water-salted HDM allergens produced by I.I. Mechnikov Biomed (Russia) under an accelerated scheme for 3 years. To assess the severity of the disease, the SCORAD indices, the Investigators Global Assessment (IGA), and the dermatological quality of life index (DLQI) were used.
 RESULTS:Patients with sensitization to major allergens ofD. farinaeand/orD. pteronyssinusDer p 1 (f 1) and/or Der p 2 (f 2) more often achieved a significant improvement of AD symptoms according to the SCORAD index (OR 3.929, 95% CI: 0.879; 17.56), as well as they more often achieved IGA values of 1 or 0 after three courses of ASIT (OR 3.556, CI 95% 0.73017.324) and more often assessed the effectiveness of ASIT as excellent and good in comparison with patients without sensitization to these components. The median and interquartile range of the DLQI index before treatment in group 1 was 17 [14; 20] points, in group 2 14 [12; 18], after the 3rdcourse of ASIT: 6 [2; 10] and 8 [3; 10] points in groups 1 and 2, respectively. Adverse events were rare, their frequency did not significantly differ in both groups.
 CONCLUSION:ASIT with HDM allergens is an effective and safe method of treatment of AD patients. Determination of the molecular spectrum of sensitization to HDM allergens components allows to justify the indications and predict the effectiveness of ASIT.

Paradoxical Response to Cold Dry Air Provocation according to the Season in Allergic Rhinitis Patients

Background and Objectives We investigated the seasonal variation of nonspecific hyperreactivity by performing the cold dry air (CDA) provocation test in both summer and winter in patients with rhinitis. Subjects and Method We performed the CDA provocation test in 57 patients with allergic rhinitis (AR) or non-allergic rhinitis (NAR). Depending on the season and the type of rhinitis, we divided patients into four groups (Summer AR group, n=17; Winter AR group, n=15; Summer NAR group, n=18 and Winter NAR group, n=7) and compared the changes in nasal symptoms, total nasal volume (TNV), and minimal cross-sectional area (MCA) measured by acoustic rhinometry after CDA provocation in each group. Results When the CDA provocation was performed for AR patients in summer, nasal symptoms improved slightly, which was significantly different from those shown in winter (Summer AR vs. Winter AR, p=0.012). In addition, there was a significant difference in symptom change between AR and NAR patients in the summer (Summer AR vs. Summer NAR, p=0.033). There was no significant difference in TNV or MCA changes after CDA provocation depending on the type of rhinitis and season (p＞0.05). Conclusion When performing CDA provocation in AR patients in summer, the examiner should pay attention to the possible paradoxical response. Key words: Acoustic rhinometry ㆍ Allergic rhinitis ㆍ Nasal provocation tests

Pathergy testing: prospective comparison of dermatoscopic evaluation and naked eye examination.

Pathergy phenomenon is a non-specific tissue hyperreactivity reaction due to trauma and is a minor diagnostic criterion of Behcet's disease. In this study, 100 patients with a suspicion of Behcet's disease who were referred to Cerrahpasa Medical Faculty Dermatology department between 01.11.2014 and 31.01.2015 are included. Skin pathergy tests were applied to all the patients and results were evaluated by two dermatologists separately at 48th hour, each with naked eye and with dermatoscopy. Test results were scored on a scale of 0-6. At the end of the study, score results of naked eye and dermatoscopy for doctor number 1 were statistically similar. Same results applied for doctor number 2. However, naked eye results of doctor number 1 and 2 for the same patients were significantly different from each other (p 0.0372) and with dermatoscopy examination this difference was eliminated (p > 0.05). This study revealed that naked eye evaluation of pathergy test results can yield different results among different interpreters. Use of dermatoscopy during the evaluation process decreases interobserver variation and subjectivity of the test.

ИЗМЕНЕНИЕ СОСТОЯНИЯ ГЕМОДИНАМИКИ НА ФОНЕ КУРСА СУРФАКТАНТ-ТЕРАПИИ У ПАЦИЕНТОВ С ГОРМОНАЛЬНО-ЗАВИСИМОЙ БРОНХИАЛЬНОЙ АСТМОЙ*

Non-specific hyperresponsiveness of the respiratory tract mucosa makes one of the important pathophysiological mechanisms for asthma development; it is characterized by the increased active response of the efferent system to stimuli. When this occurs, it damages the alveoli surfactant which ensures the viability of local immunity of lung tissue. Chronic respiratory failure induces changes in the cardiovascular system. The course of inhalations with a native surfactant reduces the dependence on inhalation corticosteroid. The objective of the study : to assess the effect of the course of inhalations with surfactant on the cardiovascular system in patients with hormone-dependent asthma. Materials and methods : 15 patients with asthma underwent a 70-day course of inhalation with natural surfactant based on a certain regimen (25 mg per inhalation, 21 inhalations in total) in addition to the basic therapy (inhaled corticosteroids and bronchodilators). On the 1st and 70th days of the surfactant therapy course, oscillometry was performed in order to assess macrohemodynamic parameters. Results. After the course of treatment, pulse pressure was found to increase by 26% compared to the initial level (p <0.05), the cardiac index increased by 16% (p <0.05) and the linear blood flow rate went up by 20% (p <0.05). At the same time, the pulse wave velocity decreased by 15% (p <0.05), while specific vascular resistance went down by 24% (p <0.01). This suggests that clinical remission during surfactant therapy in asthma patients is accompanied by changes in the functional state of the cardiovascular system.

Cellular Na+ handling mechanisms involved in airway smooth muscle contraction (Review).

A decrease in bronchial diameter is designated as bronchoconstriction (BC) and impedes the flow of air through the airway. Asthma is characterized by inflammation of the airways, reversible BC and nonspecific hyperreactivity. These last two symptoms are dependent on airway smooth muscle. Stimuli that trigger contraction can be characterized as chemical (neurotransmitters, cytokines and terpenoids) and physical (volume inspired, air pressure). Both stimuli activate signaling pathways by acting on membrane proteins and facilitating the passage of ions through the membrane, generating a voltage change and a subsequent depolarization. Na+ plays an important role in preserving the resting membrane potential; this ion is extracted from the cells by the Na+/K+ ATPase (NKA) or introduced into the cytoplasm by the Na+/Ca2+ exchanger (NCX). During depolarization, Na+ appears to accumulate in specific regions beneath the plasma membrane, generating local concentration gradients which determine the handling of Ca2+. At rest, the smooth muscle has a basal tone that is preserved by the continuous adjustment of intracytoplasmic concentrations of Ca2+ and Na+. At homeostasis, the Na+ concentration is primarily dependent on three structures: the NKA, the NCX and non-specific cation channels (NSCC). These three structures, their functions and the available evidence of the probable role of Na+ in asthma are described in the present review.

The relation between nonspecific hyperreactivity of the airways and atopic constitution in asthmatics.

Hyperreactivity of the airways caused by inflammation in asthmatics is the most important pathophysiological change. It represents a suitable ground that in the presence of risk factors and the drivers of asthma, asthmatic attack occurs. Atopic constitution is one of the most important risk factors for the development and expression of asthma. The aim of our study was to investigate the relationship between nonspecific airway hyperreactivity and atopic constituton in asthmatics. This retrospective analysis was conducted considering the results of nonspecific bronchoprovocative test with histamine, skin tests to inhalant allergens and total IgE levels in the serum of asthmatic patients with controlled bronchial asthma. The sample consisted of 162 asthmatics examined during one-year period. The examinees were male asthmatic patients, aged between 18 and 30 years. We found that the examinees with a pronounced non-specific hyperreactivity had more significant skin reaction to inhaled allergens and higher levels of total IgE in serum. The results of our study show that the intensity of airway hyperresponsiveness to histamine in asthmatics is directly related to atopic constitution.

Evaluation of control over the bronchial asthma in period of clinical well-being in teenagers depending on the severity of the bronchial inflammation

At the basis of a complex examination of 63 adolescents it was revealed, that the signs of local inflammation in the bronchi and the increase of their nonspecific hyperresponsiveness remained in some of patients with asthma during the clinical well-being period with the absence of clinical symptoms. It was shown that the lower than 40.0 mmol/l content of nitrogen monoxide metabolites in the condensate of exhaled air increases the likelihood of retention of control: relative risk = 4,3 (while assessing the level of control by the ACT questionnaire) and 5,5 – in the evaluation of control level by the GINA questionnaire. Due to this the basic therapy is effective in almost every child, because the minimal number of patients needed to be treated to obtain a positive result is 1,3, according to ACT and GINA tests.

Nonspecific Hyper‐reactivity and Localized Allergy: Cause of Discrepancy Between Skin Prick and Nasal Provocation Test

Disagreement between results of skin prick test (SPT) and nasal provocation tests (NPT) causes difficulty in differential diagnosis of allergic rhinitis (AR) and nonallergic rhinitis (NAR). We hypothesized this discrepancy could be due to the nonspecific hyper-reactivity (NHR) and localized allergy of the nasal cavity. Prospective pilot. Academic tertiary rhinologic practice. Sixty patients with AR and 62 with NAR were enrolled. We categorized patients according to results of SPT and NPT. We compared: (1) the clinical characteristics and severity of the disease, (2) change of minimal cross-sectional area (MCA) and total nasal volume (TNV) after normal saline (NS) challenge, and (3) change of nasal symptoms and acoustic parameters after intranasal house dust mite (HDM) challenge between groups. Patients in groups A (SPT[+]/NPT[+]) and C (SPT[-]/NPT[+]) complained of more persistent discomfort than those in groups B (SPT[+]/NPT[-]) and D (SPT[-]/NPT[-]). The proportion of moderate to severe symptoms was significantly higher in groups A, B, and C compared to group D. After NS challenge, MCA/TNV showed a significantly greater decrease in groups A (MCA: 27.6% ± 21.3%, TNV: 24.6% ± 16.4%) and C (MCA: 31.2% ± 24.0%, TNV: 24.1% ± 23.4%) compared to groups B (MCA: 0.1% ± 13.2%, TNV: 3.9% ± 13.5%) and D (MCA: 2.1% ± 12.1%, TNV: 2.0% ± 17.2%) (P < .05). After HDM challenge, groups A/B showed a greater decrease in MCA (Group A: 62.4% ± 16.1%, Group B: 6.4% ± 11.3%) compared to groups C/D (Group C: 45.5% ± 14.4%, Group D: -3.0% ± 9.5%). NHR and/or localized allergy should be considered in patients with rhinitis whose SPT and NPT results are not in agreement.

Emerging airway smooth muscle targets to treat asthma

Asthma is characterized in part by variable airflow obstruction and non-specific hyperresponsiveness to a variety of bronchoconstrictors, both of which are mediated by the airway smooth muscle (ASM). The ASM is also involved in the airway inflammation and airway wall remodeling observed in asthma. For all these reasons, the ASM provides an important target for the treatment of asthma. Several classes of drugs were developed decades ago which targeted the ASM – including β-agonists, anti-cholinergics, anti-histamines and anti-leukotrienes – but no substantially new class of drug has appeared recently. In this review, we summarize the on-going work of several laboratories aimed at producing novel targets and/or tools for the treatment of asthma. These range from receptors and ion channels on the ASM plasmalemma, to intracellular effectors (particularly those related to cyclic nucleotide signaling, calcium-homeostasis and phosphorylation cascades), to anti-IgE therapy and outright destruction of the ASM itself.

Nasal obstruction and rhinorrhea reflect nonspecific nasal hyper-reactivity as evaluated by cold dry air provocation

Conclusion: Nasal obstruction, rhinorrhea, and the amount of rhinorrhea that confidently reflect the parasympathetic stimulation can be used to more precisely predict nonspecific nasal hyper-reactivity (NHR). Objective: We aimed to identify factors that confidently reflected the presence and the degree of NHR, measured by cold dry air (CDA) provocation and acoustic rhinometry. Methods: A total of 156 patients with allergic or non-allergic rhinitis were classified into three groups according to the decrease of minimal cross-sectional area (MCA) after CDA provocation (group A: n = 40, MCA decrease >60%; group B: n = 29, MCA decrease 30–60%; group C: n = 87, MCA decrease <29%). Symptom scores using the visual analog scale (VAS) were obtained before and after CDA provocation. Changes of VAS were compared between groups. The amount of rhinorrhea was measured after CDA provocation. Results: VAS scores for nasal obstruction, rhinorrhea, and sneezing were significantly higher in groups A and B than in group C before and after CDA provocation. Change of nasal obstruction and rhinorrhea was significantly larger in group A compared with group B or C. There were also significant differences in the amount of rhinorrhea between groups. All these parameters significantly correlated with the change of MCA values after CDA provocation.

59 Hyperosmolar Conjunctival Provocation Test (HCPT) in the Evaluation of Ocular Symptoms

BackgroundNon-allergic environmental factors may cause ocular symptoms in atopic and non atopic subjects, which are known as nonspecific conjunctival hyperreactivity (CHR). This study aims to investigate the presence of CHR to the HCPT in subjects with ocular symptoms.Methods63 adults with ocular symptoms (itching, red eyes or tearing) were selected and tested for allergy to house dust mites and grass pollen by skin prick tests (ALK Abelló) and serum specific IgE (Immunocap-Phadia). They were considered atopic if these tests were positive to at least one allergen and non atopic if tests were negative. HCPT with 10-fold serial diluted glucose solutions was performed in all subjects until it produced conjunctival redness. Digital images were analyzed by 2 investigators (MD and technician) registering redness of the challenged eyes in red and the total area of contra-lateral eyes in blue using the fine brush tool (software GIMP 2.6.5). The number of red dots of the affected eye (%) was compared to the number of blue dots of the control eye.ResultsTPCH was positive in 33/38 atopic subjects (87%) and in 4/25 non atopic (16%). Most reactions occurred at the 40% glucose solution. Sensitivity was 87% and specificity 84% (P < 0.0001). There was a significant correlation (96.5%, Pearson, P < 0.0001) between the number of red dots reported by investigators in 23 digitalized images.ConclusionsTPCH identifies CHR in both atopic and non atopic subjects. Atopic subjects exhibit CHR more frequently than non-atopic subjects. Digital images may be useful for grading ocular hyperemia in TPCH.

Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific Immunoglobulin-E

BackgroundSkin prick test (SPT) and fluorescence enzyme immunoassay (FEIA) are widely used for the diagnosis of Immunoglobulin-E (IgE)-mediated allergic disease. Basophil activation test (BAT) could obviate disadvantages of SPT and FEIA. However, it is not known whether BAT gives similar results as SPT or FEIA for aeroallergens.ObjectivesIn this study, we compared the results of SPT, BAT and FEIA for different aeroallergens.MethodsWe performed BAT, SPT and FEIA in 41 atopic subjects (symptomatic and with positive SPT for at least 1 of 9 common aeroallergens) and 31 non-atopic subjects (asymptomatic and with negative SPT).ResultsCorrelations between SPT and BAT, SPT and FEIA, and BAT and FEIA results were statistically significant but imperfect. Using SPT as the "gold standard", BAT and FEIA were similar in sensitivity. However, BAT had lower specificity than FEIA. False positive (BATposSPTneg) results were frequent in those atopic subjects who were allergic by SPT to a different allergen and rare in non-atopic subjects. The false positivity in atopic subjects was due in part to high levels of serum Total-IgE (T-IgE) levels in atopic individuals that lead to basophil activation upon staining with fluorochrome-labeled anti-IgE.ConclusionAs an alternative to SPT in persons allergic to aeroallergens, BAT in its present form is useful for distinguishing atopic from non-atopic persons. However, BAT in its present form is less specific than FEIA when determining the allergen which a patient is allergic to. This is due to IgE staining-induced activation of atopic person's basophils and/or nonspecific hyperreactivity of atopic person's basophils.

Usefulness of the Subjective Cold Hyperresponsiveness Scale as Evaluated by Cold Dry Air Provocation

There is still no study about the correlation between the symptom score and the reactivity to cold dry air (CDA). The authors developed a subjective cold hyperresponsiveness (SCH) scale for CDA and we evaluated its usefulness by comparing the changes of the symptom score and the acoustic parameters between different SCH groups and analyzing the correlation between the SCH scale and other parameters. One hundred fifty-two patients were classified according to their SCH scale. The symptom score by the visual analog scale (VAS), the total nasal volume (TNV), and the minimal cross-sectional area (MCA) by acoustic rhinometry were obtained before and after CDA provocation. Changes of these values were compared between groups and an analysis was performed for the correlation between SCH scale and change of the VAS, TNV, or MCA. The patients with SCH grade 2 or 3 had a greater change of the VAS scores for nasal obstruction and rhinorrhea. The patients with SCH grade 2 or 3 had a greater change of the TNV (grade 0, 26.1 ± 17.2%; grade 1, 33.3 ± 26.5%, versus grade 2, 44.2 ± 30.0%; grade 3, 61.6 ± 40.0%; p < 0.05) and MCA (grade 0, 23.0 ± 25.3%; grade 1, 35.7 ± 51.1%, versus grade 2, 61.2 ± 72.4%; grade 3, 80.5 ± 56.4%; p < 0.05). Significant correlation existed between the SCH scale and changes in the TNV or MCA. We developed the SCH scale and proved its usefulness for evaluating nonspecific hyperreactivity.

Protease-activated receptor 2–dependent fluid secretion from airway submucosal glands by house dust mite extract

The submucosal gland (SMG) is important in the control of airway surface fluid. Protease-activated receptor (PAR) 2 contributes to the pathophysiology of allergies in response to nonspecific allergens bearing proteases and anion secretion. House dust mites (HDMs) have abundant proteases that can activate PAR2, but little is known about the direct effect of HDM on SMG secretion. The aim of this study was to investigate the effect of HDMs on glandular secretion and its mechanism in allergic patients, patients with chronic rhinosinusitis (CRS), or both. Inferior nasal turbinates were harvested from 55 patients and classified into 4 groups (the control, allergic rhinitis [AR], CRS, and AR+CRS groups). Amicroscope attached to a digital camera was used to quantify mucus bubbles from individual SMGs while stimulated with HDM extract, PAR2-activating peptide, and carbachol. PAR2 expression in the SMGwas determined by means of immunostaining with anti-PAR2 mAb. HDM induced a significantly higher secretion rate and number of responding glands in the AR and AR+CRS groups than in the control group. Interestingly, patients in the CRS group, who had no HDM-specific IgE antibody, showed a higher response than the control group, and its response was suppressed by a PAR2-selective antagonist. The responses to PAR2-activating peptide were similar to those to HDM, and their secretion rates positively correlated with HDM responses. PAR2 was highly expressed in all 3 disease groups with immunostaining. HDM allergens can induce glandular secretion in patients with AR, CRS, or both, and PAR2 represents a possible mechanism for nonspecific hyperreactivity in inflammatory airway diseases.

Corneal Confocal Microscopy in Patients with Vernal Keratoconjunctivitis

To compare corneal morphologic features using in vivo confocal microscopy in vernal keratoconjunctivitis (VKC) patients compared with normal subjects. Prospective, comparative study. Thirty-two VKC patients (26 males, 6 females; mean age, 17.1 years) and 40 normal subjects (20 males, 20 females; mean age, 19.3 years) were included. All subjects underwent a full ophthalmologic examination. Confoscan CS4 (Nidek, Gamagori, Japan) images of the central cornea were obtained with a ×40 noncontact lens and Z-ring device. The superficial and basal epithelium, subbasal nerve plexus, anterior stroma, stromal nerves, and endothelium of the central cornea were studied. The VKC patients had increased diameter, reflectivity, and presence of nuclear activation of superficial epithelial cells; reduced density of the basal membrane; lower density of keratocytes, increased presence of activated keratocytes, and inflammatory cells in the anterior stroma; and lower density and number of fibers, lower number of beadings, and higher grade of tortuosity of fibers in the subbasal nerve plexus. Increased alterations in thickness, deflections, and tortuosity were observed in stromal corneal nerves. An increased number of inflammatory cells in close proximity to the subbasal and stromal nerve fibers also was observed in VKC subjects. Corneal involvement in VKC is associated with alterations of the epithelium and subbasal and stromal corneal nerves. These changes may relate to the tear dysfunction and nonspecific hyperreactivity typical of these patients. Corneal confocal microscopy is a useful tool for studying in vivo pathologic corneal changes in VKC.