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Salivary pH is associated with esophageal acid reflux and neutralization of esophageal acid. In this study, we assessed the association between nocturnal decline of salivary pH and airway hyperresponsiveness. Salivary pH was serially assessed in 9 patients with mild asthma (7 men and 2 women; mean age 33.3 years; mean %predicted FEV(1.0) 89.4%) and 10 healthy volunteers (6 men and 4 women; mean age 31.2 years) using a pH indicator tape. The buffering capacity of saliva was defined as the median effective dose (ED(50)) for acidification of saliva with 0.01 N HCl, and airway responsiveness was defined as the dose of methacholine producing a 35% fall in Grs (PD(35)-Grs). There was a significant correlation between the values obtained from the pH indicator tape and those obtained from the electrometric pH meter. Using the indicator tape for sequential monitoring, we observed a nocturnal fall (ΔpH) in salivary pH in all subjects. A significant correlation was found between airway hyperresponsiveness (PD(35)-Grs) and either ΔpH or ED(50) in mildly asthmatic patients. Vagal reflux dysfunction might contribute to nocturnal salivary pH as well as to airway hyperresponsiveness in mild asthmatics.

Food or environmental allergens play a significant pathogenic role in a subgroup of patients with atopic dermatitis (AD) and can trigger eczema flares. This review focuses on when and which diagnostic and allergen-avoidance measures are beneficial. Diagnosis of allergic triggers may be aided by skin-prick tests measuring serum-specific IgE and/or atopy patch tests (APT) based on the patient's history, and when necessary, oral food challenges (OFC). In a subset of patients, therapeutic measures, such as elimination of the incriminated allergen(s), can lead to marked improvement of AD; this is especially true for food allergens, but can also apply to inhalant allergens., (Copyright 2010 Elsevier Inc. All rights reserved.)

Saliva eosinophil cationic protein (ECP) is higher in asthmatic adults than in healthy ones. However, its relationship with asthma severity, other atopic conditions and allergic sensitization have not been reported. Saliva collection is painless, readily acceptable to children and parents, and can be a potentially useful body fluid to measure asthma biomarkers. We recruited 102 physician-diagnosed young asthmatic subjects from outpatient clinics with change in FEV(1) > or = 12% with inhaled salbutamol and collected data on asthma severity, concurrent allergic rhinitis (AR) and atopic dermatitis (AD), and medication used (bronchodilator and corticosteroid). We measured whole saliva and serum ECP and performed skin prick tests (SPT) for three dust mites (Dermatophagoides pteronyssisinus, Dermatophagoides farinae and Blomia tropicalis) and two cockroaches (Periplaneta americana and Blatella germanica). Median salivary ECP was 84.6 microg/l (inter-quartile range [IQR]: 40.9-147.9) and median serum ECP was 14.7 microg/l (IQR: 6.4-32.1). Serum ECP was only higher in children whose sleep was disturbed by asthma in the past year than those who were not (geometric mean [GM]: 18.9 vs. 11.1 microg/l, relative mean difference [RMD]: 1.71 [95%CI: 1.09-2.69]). Serum ECP was increased among asthmatic children on inhaled corticosteroid than those not using them (GM: 15.6 vs. 8.1 microg/l, RMD: 1.93 [95%CI: 1.11-3.39]). Salivary ECP was not associated with asthma severity, concurrence of atopic conditions, medications used, or any SPT parameter. Saliva ECP did not correlate with serum ECP (r(s) = 0.032, p = 0.790). Salivary and serum ECP did not correlate with wheal size for any skin prick test.

Background: Animal-derived proteins are implicated in primary food allergies, but also in inhalant allergies with secondary food allergy symptoms. The objective of this study was to define the allergen(s) implicated in a case of food allergy to chicken meat, which developed in a person previously sensitized to pork after occupational exposure., Methods: A 42-year-old female with a history of occupational inhalant allergy to pork reported rhinitis, asthma, dysphonia and conjunctivitis 30 min after ingestion of chicken. Skin tests were positive to chicken meat. Protein extracts were prepared from chicken meat. Allergens were characterized by IgE immunoblotting, N-terminal sequencing and ELISA., Results: The patient showed specific IgE binding to chicken meat proteins at 12, 14, 26, 55 and 65 kDa. N-terminal amino acid sequencing identified the 12- and 14-kDa proteins as the alpha- and beta-chain of hemoglobin. ELISA and immunoblot showed specific IgE binding to hemoglobin purified from chicken blood. IgE antibodies to chicken serum albumin were detected by ELISA. Inhibition studies with chicken and porcine hemoglobin as well as with serum albumins demonstrated cross-reactive IgE antibodies., Conclusions: We report a case of confirmed occupational inhalant allergy due to pork followed by food allergy to pork and 3 years later by food allergy to chicken. Porcine and chicken hemoglobin were found to be cross-reactive allergens. Cross-reactivity between porcine and chicken serum albumin was possibly linked to a prior sensitization to cat serum albumin., (2009 S. Karger AG, Basel.)

In this study, we investigated possible separate effects of H+ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic - normoxic) ventilation over (hypoxic - normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic - normoxic) ventilation over (logPa(O2) hypoxia - logPa(O2) normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal Po2 to approximately 50 Torr lasting 5 min each at three different constant end-tidal Pco2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa(CO2), and a parallel leftward shift of the ventilatory CO2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arterial [H+] ([H+](a)) to higher values of [H+](a) without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H+ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H+](a) response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated.

We previously reported an association between relative L-ficolin deficiency and recurrent respiratory infections co-existing with allergic disorders in children. To confirm and extend this preliminary finding, we performed a prospective study on children of a similar age (mean 8.9 years) designed to establish whether the principal relationship was with infection or allergy. Serum L-ficolin values in healthy children were normally distributed with a mean value of 3838 ng/ml. L-ficolin concentrations were generally lower in patients with asthma and/or allergic rhinitis with (mean 3413 ng/ml; p=0.02) or without (3512 ng/ml; p<0.07) respiratory infections, but not in patients with respiratory infections without allergic disease (3623 ng/ml; p=0.2). The lower average values in the group comprised of children with respiratory allergy and infections were largely due to a high proportion of very low values: 18.3% had values below 2150 ng/ml compared to only 5.5% of healthy controls (OR=3.9; p=0.01). This relationship was not apparent in the groups characterized by allergy without infection or infections without allergy. An association between mannan-binding lectin (MBL) insufficiency and recurrent respiratory infections was also confirmed. One of the patients was MASP-2 deficient, evidenced both by MASP2 genotyping and by lectin pathway activity measurement. In conclusion, L-ficolin may confer some protection from microorganisms that exacerbate allergic inflammation in the lung and its relative deficiency may contribute to enhanced susceptibility to respiratory infections. MBL insufficiency and MASP-2 deficiency are risk factors for recurrence of infections independently of allergic disease.

Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in sensing molecular patterns and in programming adaptive T cell responses. Here we show that in vivo activation of TLR4 by house dust mite antigens leads to the induction of allergic disease, a process that is associated with expression of a unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)-126 suppressed the asthmatic phenotype, resulting in diminished T(H)2 responses, inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus hypersecretion. miR-126 blockade resulted in augmented expression of POU domain class 2 associating factor 1, which activates the transcription factor PU.1 that alters T(H)2 cell function via negative regulation of GATA3 expression. In summary, this study presents a functional connection between miRNA expression and asthma pathogenesis, and our data suggest that targeting miRNA in the airways may lead to anti-inflammatory treatments for allergic asthma.

Background: A history of atopic respiratory conditions has been linked to an increased risk of stroke. What remains unclear is whether positive allergy skin testing is associated with an increased risk of stroke. The primary goal of this study was to determine whether positive allergy skin testing is associated with an increased risk of fatal stroke. A secondary goal is to determine whether having both positive allergy skin testing and an atopic respiratory condition is associated with a particularly high risk of stroke death., Methods: An analysis was performed of the National Health and Nutrition Examination Survey II Mortality Cohort., Results: Controlling for age, gender, race, alcohol use, smoking status, diabetes, hypertension, and body mass index, patients with positive allergy skin testing had a hazard ratio for stroke mortality of 1.56 (95% CI, 1.01-2.40) versus those without positive allergy testing. Patients with both positive allergy testing and an atopic respiratory condition had a hazard ratio for stroke mortality of 2.31 (95% CI, 1.13-4.73)., Conclusions: Individuals with both positive allergy skin testing and an atopic respiratory condition have more than a 2-fold increased risk of fatal stroke. This novel risk factor has substantial implications for a large segment of the population not previously considered at risk.

Background: Diseases in the upper and lower airways often occur concomitantly, and evidence indicates a close relationship between them. Optimal treatment of airway disease requires knowledge about this relationship; the article presents an updated overview of the field., Material and Methods: This paper is based on extensive clinical experience with airway disease, own research and literature studies., Results: It is well documented that patients suffering from asthma have rhinitis more often than those without. Likewise, those suffering from nose and sinus disease, e.g. allergic rhinitis, sinusitis and nasal polyposis, have an increased incidence of asthma. Treatment of disorders in one airway compartment often has a positive impact on the airways in general., Interpretation: Disorders in the upper and lower airways should be considered as the same disease to a larger extent than they are today. Patients with disease in one airway compartment should be considered for pathology elsewhere in the airways. Therapeutically, the airways should be regarded as one entity.

Purpose: To investigate the possible role of nasal allergy on hearing levels in chronic otitis media with effusion (OME)., Method: In 87 adults who had chronic OME, 185 nasal challenges with allergen were performed using rhinomanometry combined with tympanometry and pure-tone audiometry (PTA)., Results: Of the 87 patients, 71 developed 131 positive nasal responses (NRs; p < 0.01), 119 of which were associated with significant changes in middle ear pressure (p < 0.01) and 96 with significant changes in PTA (p < 0.01). The hearing threshold increased significantly (>30 dB) at tone frequencies of 2,000 Hz during 63 NRs (p < 0.05) and at tone frequencies of 4,000 Hz during 93 NRs (p < 0.01)., Conclusion: Nasal allergy can affect Eustachian tube function, leading to the changes in the middle ear pressure and resulting in hearing impairment. Nasal challenges with allergen performed using rhinomanometry combined with tympanometry and PTA may be a useful diagnostic supplement in chronic OME patients.

Background: Staphylococcus aureus (SA) in the nose can be a simple colonizer but also may create an intramucosal reservoir causing recurrent infections or can be a specific immune modulator through superantigenic mechanisms. Because the colonization rate of SA is high, but immunologic reactions causing chronic disease are less frequent, the purpose of this study was to identify the presence of intramucosal SA in healthy subjects and in patients with chronic rhinosinusitis (CRS) and to eventually relate those to the specific immunologic changes due to SA enterotoxins., Methods: Nasal tissue was collected in 40 subjects (9 controls, 21 CRS patients with [CRSwNP], and 10 CRS patients without nasal polyps [CRSsNP]). Tissues were homogenized, and mediators and specific IgE-antibodies against SA enterotoxins (SAE-IgE) were measured using the UniCAP system. The tissue was analyzed for the presence of SA by the peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) technique (AdvanDx), and a semiquantitative scoring system was applied. Mann-Whitney exact test was used for statistical analysis., Results: SA in the mucosal tissue was detected in a higher quantity among CRSwNP subjects with aspirin exacerbated respiratory disease (AERD) versus controls and CRSsNP (p=0.03). Among CRSwNP patients, Th2 markers (eosinophil cationic protein, p=0.006, and total IgE, p=0.004) were increased related to the SAE-IgE status but not related to the presence of SA in the tissue., Conclusion: This study describes the detection of SA within nasal tissue using the PNA-FISH technique. The presence of SA in the submucosa did not correlate with the amplification of the Th2-related inflammation typically found in CRSwNP patients, but this reaction is dependent on the formation of SAE-IgE within mucosal tissue. We also show, for the first time, that submucosal SA is a prevalent finding in CRSwNP patients with AERD.

Background: Lupin, a legume with good nutritional value, is used in food production today, most often in bakery products. Lupin sensitization is often seen among patients with reactions to legumes, but the number of reports describing lupin anaphylaxis is also increasing., Objective: To investigate the occurrence of lupin sensitization, cross-reactivity, and lupin allergy among patients with suspected food allergy in Finland, where lupin is a labeled ingredient in few products., Methods: The occurrence of positive skin prick test (SPT) reactions to lupin seed flour was studied among 1522 patients with suspected food allergy from November 1, 2005, through December 31, 2007. Clinical histories and diagnostic SPT results were analyzed among patients with positive SPT results to lupin. For 1 patient, ImmunoSpot and lupin radioallergosorbent test inhibition methods were used., Results: Lupin sensitization was shown in 25 of 1522 patients (1.6%), and probable lupin allergy was diagnosed in 7 of 25 patients, in whom the clinical symptoms varied from anaphylaxis and respiratory symptoms to contact urticaria and itchy mouth. Cross-reactions or concurrent reactions to other legumes were seen in 18 of 25 patients., Conclusions: Clinically relevant lupin allergy often occurs in patients without atopic background or other food allergies, although lupin sensitization most commonly seems to represent cross-reactivity to other legumes. The occurrence of lupin allergy in a country where lupin has not been traditionally used is surprisingly common, suggesting that short-term use of modest amounts of lupin can cause serious allergic reactions.

Background: Atrial natriuretic peptide (ANP) and its receptor, NPRA, have been extensively studied in terms of cardiovascular effects. We have found that the ANP-NPRA signaling pathway is also involved in airway allergic inflammation and asthma. ANP, a C-terminal peptide (amino acid 99-126) of pro-atrial natriuretic factor (proANF) and a recombinant peptide, NP73-102 (amino acid 73-102 of proANF) have been reported to induce bronchoprotective effects in a mouse model of allergic asthma. In this report, we evaluated the effects of vessel dilator (VD), another N-terminal natriuretic peptide covering amino acids 31-67 of proANF, on acute lung inflammation in a mouse model of allergic asthma., Methods: A549 cells were transfected with pVD or the pVAX1 control plasmid and cells were collected 24 hrs after transfection to analyze the effect of VD on inactivation of the extracellular-signal regulated receptor kinase (ERK1/2) through western blot. Luciferase assay, western blot and RT-PCR were also performed to analyze the effect of VD on NPRA expression. For determination of VD's attenuation of lung inflammation, BALB/c mice were sensitized and challenged with ovalbumin and then treated intranasally with chitosan nanoparticles containing pVD. Parameters of airway inflammation, such as airway hyperreactivity, proinflammatory cytokine levels, eosinophil recruitment and lung histopathology were compared with control mice receiving nanoparticles containing pVAX1 control plasmid., Results: pVD nanoparticles inactivated ERK1/2 and downregulated NPRA expression in vitro, and intranasal treatment with pVD nanoparticles protected mice from airway inflammation., Conclusion: VD's modulation of airway inflammation may result from its inactivation of ERK1/2 and downregulation of NPRA expression. Chitosan nanoparticles containing pVD may be therapeutically effective in preventing allergic airway inflammation.

The relationship between allergic airway inflammation and pneumococcal pneumonia is not well understood. We assessed susceptibility to experimental pneumococcal pneumonia in mice with and without allergic airway inflammation. Susceptibility to pneumococcal pneumonia was evaluated by challenging mice with a bioluminescent Streptococcus pneumoniae strain after sensitization with ovalbumin (OVA), with subsequent monitoring of pneumococcal infection using real-time photonic imaging. Of 46 OVA-sensitized mice challenged with pneumococci, 13 (28%) developed imaging findings consistent with pneumococcal pneumonia. In comparison, 28 (57%) of 49 non-sensitized control mice developed pneumococcal pneumonia (P = 0.005). While none of the control group developed meningitis (0%, none of 28), two mice in the OVA-sensitized group developed meningitis (15.4%, two of 13) (P = 0.09). The mean bacterial count in the lung was significantly lower in the OVA-sensitized than the non-sensitized group (8.26 +/- 0.69 versus 9.21 +/- 0.67 log(10) colony-forming units (CFU)/g, P = 0.002). There was a trend towards the mean bacterial count in the spleen being higher in the OVA-sensitized versus the non-sensitized group (8.14 +/- 0.89 versus 7.45 +/- 1.07 log(10) CFU/g, P = 0.071). A high level of interleukin (IL)-4 in lung homogenates was associated with risk of pneumococcal infection independent of sensitization with OVA (odds ratio: 49.7, 95% confidence interval 2.92-846.5, per increment of 1.0 pg/ml). In the murine model studied, acute allergic airway inflammation reduced susceptibility to pneumococcal pneumonia. IL-4 may increase the risk of pneumococcal pneumonia independently of allergic airway inflammation.

A 17-year-old patient was transferred to the emergency room with an impacted food bolus by colleagues from the Department of Otorhinolaryngology. The examination of ear, nose and throat revealed significant amounts of saliva in both recessus piriformis, a radiologic examination of the esophagus showed a foreign body with a diameter of 1.6 cm in the region of the transitional zone of esophagus and stomach with a support level of the contrast medium. Clinical examination and laboratory tests showed no abnormalities. An emergency gastroscopy was performed. The foreign body, already evident in the barium swallow, was found in the distal esophagus. The foreign body was identified as a food bolus and gently advanced into the stomach with the aid of the gastroscope. In the stomach further food residues were detected and the examination was aborted because of increased risk of aspiration. On the next day, an elective gastroscopy was performed. Several biopsies were obtained from the esophagus because eosinophilic esophagitis (EE) was suspected due to clinical symptoms. Histological work-up showed a significant amount of eosinophilic granulocytes (> 15 eosinophils/HPF, 400 x) and reactive changes in the distal esophagus. Therefore, EE was diagnosed. Fluticasone therapy led to amelioration of symptoms and there was no evidence of recurring bolus impaction during follow-up.

gammadelta T cells regulate airway reactivity, but their role in ozone (O3)-induced airway hyperresponsiveness (AHR) is not known. Our objective was to determine the role of gammadelta T cells in O3-induced AHR. Different strains of mice, including those that were genetically manipulated or antibody-depleted to render them deficient in total gammadelta T cells or specific subsets of gammadelta T cells, were exposed to 2.0 ppm of O3 for 3 hours. Airway reactivity to inhaled methacholine, airway inflammation, and epithelial cell damage were monitored. Exposure of C57BL/6 mice to O3 resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR-delta(-/-) mice did not develop AHR, although they exhibited an increase in neutrophils and epithelial cells in the lavage fluid. Similarly, depletion of gammadelta T cells in wild-type mice suppressed O3-induced AHR without influencing airway inflammation or epithelial damage. Depletion of Vgamma1+, but not of Vgamma4+ T cells, reduced O3-induced AHR, and transfer of total gammadelta T cells or Vgamma1+ T cells to TCR-delta(-/-) mice restored AHR. After transfer of Vgamma1+ cells to TCR-delta(-/-) mice, restoration of AHR after O3 exposure was blocked by anti-TNF-alpha. However, AHR could be restored in TCR-delta(-/-)mice by transfer of gammadelta T cells from TNF-alpha-deficient mice, indicating that another cell type was the source of TNF-alpha. These results demonstrate that TNF-alpha and activation of Vgamma1+ gammadelta T cells are required for the development of AHR after O3 exposure.

Endogenous relaxin has recently been demonstrated to protect the airway/lung against age-related fibrosis and against inflammation-associated airway fibrosis in animal models of allergic airways disease (AAD). In the current study, we examined the contribution of the primary relaxin receptor, relaxin family peptide receptor-1 (RXFP1), in mediating these effects of relaxin. Lung tissues from healthy aging RXFP1 gene-knockout (Rxfp1(-/-)) and wild-type (Rxfp1(+/+)) mice and from 8- to 10-wk-old Rxfp1(-/-) and Rxfp1(+/+) mice subjected to a mouse model of AAD were assessed for various markers of airway fibrosis and remodeling. Male and female Rxfp1(-/-) mice demonstrated an age-related progression of airway/lung fibrosis. Saline-treated Rxfp1(-/-) mice had significantly increased myofibroblast differentiation and lung collagen deposition (both P < 0.05), decreased matrix metalloproteinase (MMP)-9 expression and activity (P < 0.05), but equivalent levels of MMP-2 and tissue inhibitor of metalloproteinases (TIMPs) to that measured in saline-treated Rxfp1(+/+) mice. As expected, ovalbumin (OVA)-treated Rxfp1(+/+) mice developed markedly increased lung myofibroblast differentiation and collagen deposition (both P < 0.01 vs saline-treated Rxfp1(+/+) mice), significantly decreased lung MMP-2 and MMP-9 expression and activity and increased TIMP-1 expression (all P < 0.05 vs. respective measurements from saline-treated Rxfp1(+/+) mice). Surprisingly, however, OVA-treated Rxfp1(-/-) animals had equivalent levels of airway fibrosis and gelatinase activity but increased TIMP-1 expression (P < 0.05) compared with OVA-treated Rxfp1(+/+) mice. These combined findings demonstrate that RXFP1 is involved in mediating relaxin's effects on airway fibrosis during homeostasis but not during inflammation-induced fibrosis associated with chronic AAD.

Cavernous sinus thrombosis (CST) is a rare and serious complication secondary to invasive fungal sinusitis, but rarer still in cases of allergic fungal sinusitis. Current recommendations for cavernous sinus thrombosis are controversial, especially regarding anticoagulation, secondary to the rarity of the diagnosis. Early surgical debridement and intravenous antibiotics are crucial to prevent mortality and decrease morbidity. Because thrombosis is thought to be caused by a bacterial superinfection, which follows a response to Aspergillus, antifungals may not be necessary. Despite the controversy, most physicians opt to treat with anticoagulation.

Objective: Air pollution can promote airway inflammation, posing significant health risks for children with chronic respiratory problems. However, it is unknown whether this process is reversible, so that limiting pollution will benefit these children. We measured the short-term response of allergic asthmatic children exposed to a real-life reduction in outdoor air pollution by using noninvasive biomarkers of airway inflammation and function., Patients and Methods: Thirty-seven untreated allergic children with mild persistent asthma were recruited from a highly polluted urban environment and relocated to a less polluted rural environment. Air pollution, pollen counts, and meteorological conditions were carefully monitored at both sites. Nasal eosinophils, fractional exhaled nitric oxide, peak expiratory flow, and urinary leukotriene E(4) were measured first in the urban environment and then again 7 days after relocation to the rural environment., Results: One week after relocation to the rural environment, we measured, on average, a fourfold decrease in nasal eosinophils and significant decrease in fractional exhaled nitric oxide. We also noted an improvement in lower airway function, reflected by highly significant increase in peak expiratory flow. In contrast, mean urinary leukotriene E(4) concentration remained unchanged after 1 week of exposure to the rural environment., Conclusions: Better air quality is associated with a rapid reduction of airway inflammation in allergic asthmatic children. Nasal eosinophils and fractional exhaled nitric oxide are sensitive indicators of this effect, and their rapid decline is paralleled by improved airway function measured by peak expiratory flow. Leukotriene synthesis has a more variable response to environmental modifications.

Eosinophilic esophagitis (EoE) is a newly recognized disease and is an emerging entity throughout developing and developed countries, including the United States. Therefore, understanding the causes, natural history, diagnosis, and management is important for future therapeutic interventions. The pathogenesis of EoE is still not clear, but a growing body of evidence has established that this condition represents a T-cell-mediated immune response involving several proinflammatory mediators and chemoattractants known to regulate eosinophilic accumulation in the esophagus, such as IL-4, IL-5, IL-3 and eotaxin-1, -2, and -3. Determining the mechanism or mechanisms through which human esophageal-derived factors ultimately induce the functional abnormalities observed, and to which antigens patients who have EoE are sensitized that lead to the manifestation of symptoms, is of significant interest.

Objective: To determine whether patients with allergic rhinitis have altered FoxP3 gene expression and/or mutations., Study Design and Methods: We collected nasal secretions from 14 volunteers (five of whom have allergic rhinitis) and five ENT allergy patients. Total RNA was isolated from these nasal secretions. The gene expression levels of FoxP3 were quantified by both semi-quantitative RT-PCR and real-time PCR using Actin as a housekeeping gene. The cDNA fragments amplified by RT-PCR were analyzed by DNA sequencing., Results: We found that patients with allergic rhinitis had significantly lower FoxP3 mRNA compared to nonallergic controls (P < 0.01). In addition, we found a point mutation in the FoxP3 gene from a patient who not only has severe allergic rhinitis, but also has asthma. This mutation locates in a highly conserved region of FoxP3 gene and partially impaired FoxP3 functions., Conclusion: Our data indicate that either reduced FoxP3 gene expression or impaired FoxP3 functions are involved in the development of allergic disease in humans.

Asthma is a chronic inflammatory disease of airways. Approximately 40% of asthma cases can be attributed to atopy. An increased immunoglobulin E (IgE) production is the strongest predisposing factor for the development of asthma. IgE is a key component of asthma pathophysiology and contributes to both the early- and late-phase inflammatory cascade in the airways. Omalizumab is a recombinant anti-IgE monoclonal antibody developed for the treatment of allergic diseases associated with high circulating IgE levels. By reducing serum IgE levels, as well as FceRI and FceRII receptor expression on inflammatory cells, omalizumab inhibits development of inflammatory cascade. Omalizumab is currently the only IgE-targeted therapy approved by EMEA (European Agency for the Evaluation of Medicinal Products) and FDA (Food and Drug Administration) for asthma treatment. It is efficacious in the treatment of moderate-to-severe and severe persistent allergic asthma poorly controlled with regular treatment. The drug reduces symptoms, exacerbations, emergency visits, hospitalizations, inhaled and systemic corticosteroid and rescue medication requirements and improves quality of life.

Purpose: Voice problems are common in occupations with a large voice loading. Clergy are usually classified as professional voice users. The aim of our study was to investigate the prevalence of voice problems in Catholic priests and to identify some of the risk factors for their voice disorders., Methods: Questionnaires were sent to 600 randomly chosen Catholic parish priests and vicars in Slovenia to collect information on the prevalence and causes of voice disorders, vocal load, vocal habits, and certain diseases influencing voice quality. Data were analyzed for a total of 340 priests and in subgroups of priests with frequent voice disorders, priests without voice disorders, and priests over the age of 64., Results: Overall, 85.6% of the priests reported having voice problems during their career, 15.9 % of them experiencing frequent voice problems. Respiratory-tract infection was the most common cause of the voice problems. The following significant risk factors for frequent voice problems were identified: frequent throat clearing, vocal load during spare time, voice disorders during training and not receiving instruction on correct vocal technique. The priests without voice problems had experienced significantly fewer voice problems during their training and had less frequent throat clearing, less frequent asthma and fewer allergies than the other priests. Being over the age of 64 and teaching more than 10 hours each week were not identified as risk factors for voice disorders., Conclusions: The prevalence of voice disorders in Catholic priests in Slovenia is high. Respiratory-tract infection is the most common cause of their voice problems. Allergies, frequent throat clearing, not receiving instruction on correct vocal use and vocal hygiene, and a history of voice problems during training were stated as risk factors for voice disorders. In order to decrease the prevalence of voice disorders in priests and in other occupations with a large vocal load, we suggest that an ENT examination before the start of training and the inclusion of information on correct use of the voice and on diseases influencing voice quality should be included as a standard part of the educational process.

Allergic rhinitis and asthma are common among university students. Inhalant allergies have been considered to be a risk factor contributing to voice disorders. The purpose of this pilot study was to determine if students with confirmed respiratory allergies have frequently occurring vocal symptoms. A questionnaire concerning the prevalence of vocal symptoms was distributed to 49 students attending a 3-year allergen immunotherapy program and to 54 students without known allergy. The results indicated that subjects with allergy report significantly more vocal symptoms than subjects without allergy. Allergy should be considered as an underlying factor for vocal symptoms, especially for persons who work in or study for vocally demanding occupations.

Background: Overweight and obesity are major health issues in Western societies. They are related with a higher risk of different co-morbidities but their relationship with airway hyperresponsiveness (AHR) is still under discussion. Nevertheless, they are related to higher severity in asthma and other respiratory diseases. The aim of the study was to analyze the AHR in individuals with normal lung function without respiratory disorders, according to body mass index (BMI) calculation., Methods: We performed clinical observation and basal lung function tests (LFT) in 595 consecutive individuals in order to exclude respiratory disease. 377 individuals fulfilled the criteria of normal values according international guidelines. They were submitted to standardized treadmill exercise test followed by bronchodilator test. FVC, FEV1, FEF 25/75, RV and Raw were obtained at different conditions according to BMI groups (I: lean; II: normal; III: overweight; IV obese)., Results: 55.2% of the sample was overweight or obese, and a signficant relationship was found with female gender and older ages (p=0.0046 and p<0.0001 respectively). The positive response to exercise test or bronchodilator beta2 agonists was not significantly frequent compared with the other groups. In obese individuals the exercise markedly reduced basal Raw and increased FEF 25/75. Lean individuals showed higher basal values of RV that was reduced upon exercise. Response to 12 agonists showed no differences according to weight biotypes., Conclusion: BMI hampers lung function in normal individuals, and seems not to be related to AHR. Regular exercise should be encouraged in overweight and obese individuals, since it increases their bronchial permeability as shown in lower frequency of positive exercise tests. The same is advisable for lean individuals for different reasons. Their increased basal RV and Raw improve upon exercise. Despite overweight and obesity are being related to a low-grade of basal systemic inflammation, there was no association with a higher basal bronchial hyperresponsiveness in these individuals.

Purpose of Review: We aimed to review the association between atopic eczema and allergic sensitization and food allergy and its determinants on the basis of current epidemiological literature., Recent Findings: About 50% of children with atopic eczema and about 35% of adults are sensitized to common allergens. Gender, geography (e.g. East and West Germany), and socioeconomic factors determine the proportion of atopic eczema with allergic sensitization. Allergic sensitization in addition to atopic eczema obviously increases the risk for respiratory allergies. Sensitization to house dust mites seems to be important and clinically relevant for atopic eczema. Population-based studies on the association between food allergy and atopic eczema are limited. Although, up to 40% of children in hospital settings react to certain food allergens by a flare-up of their atopic eczema, there is an indication that on a population basis, adults with atopic eczema do only react occasionally with a worsening of their skin disease due to food allergens., Summary: Atopic eczema is not necessarily associated with allergic sensitization. Sensitization to house dust mites, however, seems to be clinically relevant. The impact of food allergy on atopic eczema is difficult to assess on the basis of epidemiological studies and more detailed studies are needed.

Background: The original hygiene hypothesis predicts that infections should protect against asthma but does not account for increasing evidence that certain infections might also promote asthma development. A mechanistic reconciliation of these findings has not yet emerged. In particular, the role of innate immunity in this context is unclear., Objective: We sought to test whether bacterial respiratory tract infection causes airway sensitization toward an antigen encountered in parallel and to elucidate the contribution of innate immune responses., Methods: Mice were infected with different doses of Chlamydia pneumoniae, followed by exposure to human serum albumin (HSA) and challenge with HSA 2 weeks later. Airway inflammation, immunoglobulins, and lymph node cytokines were assessed. Furthermore, adoptive transfer of dendritic cells (DCs) and depletion of regulatory T (Treg) cells was performed., Results: C pneumoniae-induced lung inflammation triggered sensitization toward HSA, resulting in eosinophilic airway inflammation after HSA challenge. Airway sensitization depended on the severity and timing of infection: low-dose infection and antigen exposure within 5 days of infection induced allergic sensitization, whereas high-dose infection or antigen exposure 10 days after infection did not. Temporal and dose-related effects reflected DC activation and could be reproduced by means of adoptive transfer of HSA-pulsed lung DCs from infected mice. MyD88 deficiency in DCs abolished antigen sensitization, and depletion of Treg cells prolonged the time window in which sensitization could occur., Conclusions: We conclude that moderate, but not severe, pulmonary bacterial infection can induce allergic sensitization to inert inhaled antigens through a mechanism that requires MyD88-dependent DC activation and is controlled by Treg cells.

There is growing evidence linking psychological stress to atopic disease, particularly asthma. Anxiety sensitivity, which is the fear of anxiety-related symptoms, may be particularly important in the study of anxiety and atopic disease. The present study examined the association between atopy and anxiety sensitivity in adult asthmatics. A total of 217 asthma patients who had undergone standard pulmonary function and allergen skin prick testing were included. Participants completed the Anxiety Sensitivity Index, Penn State Worry Questionnaire, Type D Personality Scale-16 and Beck Depression Inventory-II on the day of their asthma clinic visit. Total Anxiety Sensitivity Index score was found to be significantly higher in atopic (M = 17.15, SE = .9) versus non-atopic (M = 12.68, SE = 1.5) asthmatics, independent of age, sex, smoking status, asthma severity, asthma duration, and anxiolytic medication use (F = 6.11, p = .014). There was no evidence for a significant association between any of the other questionnaire scores and atopic status.

Objective: Recent data suggested a relationship between carotid artery intima/media thickness and airway hyperresponsiveness (AHR). Our objective was to assess the potential relationship between AHR and coronary atherosclerosis plaque volume as assessed by 3-dimensional intravascular ultrasound (IVUS)., Methods: Thirty-six subjects had a spirometry and methacholine challenge, skin prick tests, blood sampling and induced sputum analysis., Results: We found five (13.9%) patients who presented AHR to methacholine. There was no significant difference between patients with and without AHR, in plaque volume (221 +/- 45 mm3 vs. 189 +/- 13 mm3, P = 0.4), lumen volume (187 +/- 11 mm3 vs. 221 +/- 11 mm3, P = 0.2), or in total vessel volume (377 +/- 20 mm3 vs. 415 +/- 20 mm3, P = 0.5), respectively. No relationship was found between AHR, cell counts and coronary atherosclerotic plaque, lumen or total vessel volumes. There were significantly more eosinophils (1.69 +/- 1.75% vs. 0.21 +/- 0.31%, P = 0.0007) and lymphocyte counts (3.75 +/- 1.59% vs. 2.25 +/- 1.12%, P = 0.03) in patients with AHR compared to patients without., Conclusion: In patients with stable coronary artery disease, the incidence of AHR was low and there was no relationship between AHR or airway inflammation and coronary atherosclerosis.

Many patients with chronic urticaria (CU) worry that foods or other allergens are responsible for their urticaria. Skin prick testing (SPT) may be one of the investigations used to provide a clear illustration. The purpose of our study was to assess the prevalence of positivity of SPT to food allergens and aeroallergens and their relevance in patients with CU, in order to demonstrate the diagnostic value of SPT in CU. We retrospectively reviewed case record forms of patients with chronic ordinary urticaria who underwent SPT in the Urticaria Clinic, Siriraj Hospital, during the period 2000-2004. The studied allergens included 16 food allergens and 12 aeroallergens. Eighty-eight patients were enrolled. The prevalence of positive SPT among patients with CU was 47.7%. Patients who had personal histories of atopy had statistically significant positive SPT results compared with patients who had negative SPT. Of 88 patients, 26 patients (30%) gave positive results to food allergens, 36 patients (41%) gave positive results to aeroallergens and 20 patients (22.7%) gave positive results to both food and aeroallergens. One-third of the subjects (34.6%) who had positive SPT results to food allergens had clinical relevance of food allergy in some systems but only one patient had clinical relevance of food-induced urticaria. Half of the patients who had a history of aeroallergen sensitivity gave a positive SPT response for aeroallergens; however, there was no clinical relevance to their CU. Our study showed that the prevalence of positive SPT to food allergens and aeroallergens in patients with CU was common but had little clinical relevance to CU.

The aim of this study was to estimate the incidence of anaphylaxis in the emergency department of a tertiary-care hospital, describe the clinical features and the management of the patients and determine those with mild manifestations. A retrospective study was conducted from 2005 to 2006 using anaphylaxis-related ICD-10 terms. Two different sets of criteria for the diagnosis of anaphylaxis were applied, first the criteria previously accepted by emergency practice, followed by the recent criteria set forth at the 2005 international meeting. Sixty-four patients fulfilled the previous criteria with an average incidence of 52.5 per 100,000 patients per year with a shift towards females in 2006. The most common presentations were cutaneous, followed by respiratory symptoms. Food allergy was the most common cause, especially prawn. After applying the recent criteria, 13 patients (20.4%) were excluded, which reduced the incidence to 42.2 per 100,000 patients per year. Long term follow up is suggested for the possible or mild cases that were re-categorized.

Aim: To compare the response to skin prick tests (SPTs) to food antigens (FAs) and inhalant allergens (IAs) in patients with two subtypes of irritable bowel syndrome (IBS) and healthy controls., Methods: We compared the results of SPTs for IAs and FAs in 87 volunteers divided into three groups: diarrhea predominant IBS (D-IBS) Group I (n = 19), constipation predominant IBS (C-IBS) Group II (n = 17), and normal controls Group III (n = 51)., Results: Of the 285 tests (171 for FAs and 114 for IAs) performed in Group I we obtained 45 (26.3%) positive responses for FA and 23 (20.1%) for IA. Of the 153 tests for FA in Group II, we obtained 66 (20.1%) positive responses, and of the 102 tests for IA, we obtained 20 (19.6%) positive responses. Of the 459 tests for FA performed in Group III, we obtained 39 (84%) positive responses, and of the 306 for IA, we obtained 52 (16.9%) positive responses. The numbers of positive responses were not significantly different between the three groups, but in the D-IBS group, the number of SPT FA responses differed significantly from those for the other two groups (P > 0.01)., Conclusion: Despite the small number of cases studied, the higher reactivity to FAs in Group I compared to Groups II and III adds new information, and suggests the presence of a possible alteration in intestinal epithelial function.

Objectives: Fungi, by systemic or local allergic effect, may play a role in the pathogenesis of chronic rhinosinusitis (CRS). We investigated the incidence of fungal allergy in patients with CRS and its effect on the clinical characteristics of the disease., Patients and Methods: The study included 127 patients, aged 18 years or over, with CRS (42 females, 85 males; mean age 43+/-12 years; range 19 to 78 years). Fungal allergy was determined by skin prick test and its effect was analyzed on blood eosinophil and total immunoglobulin E levels, the presence of polyps, and paranasal sinus computed tomography scores., Results: Eighty-five patients (66.9%) were found to have allergy. The incidence of allergy did not differ between patients with and without polyps (p>0.05). House dust mites (62.2%) were the most frequent allergens. The incidence of fungal allergy was 38.8% in allergic patients. Isolated fungal allergy was detected in two patients (1.6%). The most frequent fungal allergens were Aspergillus, followed by Alternaria, and Penicillium. No association was found between fungal allergy and blood eosinophil and total immunoglobulin E levels, presence of polyps, or paranasal sinus computed tomography scores (p>0.05)., Conclusion: The incidence of fungal allergy in patients with CRS was found to be high in this study. Tissue culture studies are required to determine the definitive relationship between fungal allergy and clinical features of CRS.

Background: A definitive diagnosis of aspirin-exacerbated respiratory disease (AERD) requires a positive oral aspirin challenge (OAC), but predicting which patients will have positive challenges is often difficult., Objective: To analyze information about historical aspirin- and nonsteroidal anti-inflammatory drug (NSAID)-associated respiratory reactions and clinical characteristics as potential markers to predict positive OACs., Methods: A total of 243 patients underwent OACs. Data related to previous reactions and clinical characteristics of patients were correlated with the result of the OACs., Results: Without prior exposure to aspirin or NSAIDs, the chance of a positive OAC was 5 in 12 (42%) but was 198 in 231 (86%) for those with a history of aspirin- and NSAID-associated asthma attacks. Sex, atopy, number of sinus infections per year, and number of sinus surgical procedures were not associated with positive OACs. Patients with 2 or more prior aspirin- and NSAID-associated respiratory reactions had an 89% chance of having a positive OAC vs single reactors (80%; P = .04). Mild or moderate prior reactions were associated with 84% or 80% positive OACs, whereas 100% of the 45 patients with severe prior reactions had positive OACs (P = .007). Except for hospitalizations, treatment locations of prior reactions (home or emergency department) did not seem to make any difference. Logistic regression identified age, sense of smell, and multiple prior reactions as independent risk factors associated with positive OACs., Conclusions: Age younger than 40 years, poor sense of smell, multiple prior respiratory reactions, and severe prior asthmatic reactions associated with aspirin and NSAIDs significantly increased the chances of a positive OAC.

Aim: In a general adult population, we have demonstrated an inverse association between periodontitis and respiratory allergies that is in line with the hygiene hypothesis suggesting a protective effect of infections against the development of allergies. The objective of the present study was to investigate the association between periodontitis and respiratory allergies in a type 1 diabetes mellitus population., Material and Methods: The study population comprised 170 patients with type 1 diabetes mellitus aged 17-80 years. Respiratory allergies were present in 22 subjects. The attachment loss (AL) was measured. Periodontitis was defined according to the percentage of surfaces that exceeded 3 mm AL (healthy, mild, moderate, severe periodontal conditions)., Results: Our adjusted analyses revealed an inverse association between periodontitis and respiratory allergies. For increasing AL, a trend towards a decreasing risk was present for respiratory allergies (p(trend)<0.05). Compared with subjects with healthy periodontal conditions, individuals with severe periodontal conditions had the lowest risk of respiratory allergies [odds ratios (OR) 0.06 (95% confidence interval (CI) 0.01-0.39)], followed by subjects with moderate AL [OR 0.14 (95% CI 0.03-0.63)] and mild AL [OR 0.32 (95% CI 0.09-1.08)]., Conclusion: There is a strong inverse association between periodontitis and respiratory allergies in patients with type 1 diabetes mellitus. These findings further support the hygiene hypothesis.

Several large retrospective cohort studies demonstrate that pre-eclampsia is common in asthmatics. Whether airway hyperresponsiveness (AHR), a hallmark of asthma, is associated with pre-eclampsia is unknown. We measured AHR, using a methacholine challenge, and atopy in 19 women 3-60 months postpartum following pre-eclamptic or normotensive pregnancies. The geometric mean (95% CI) concentration of methacholine required to produce a >20% fall in the forced expiratory volume in 1 second (PC20 FEV1) was 8.9 (2.2-36) mg/ml in pre-eclamptics versus 72 (32-131) mg/ml in controls (P = 0.01) and 9 (1.9-40) mg/ml in atopic pre-eclamptics without asthma versus 54 (17-174) mg/ml (P = 0.038) in matched controls. Therefore, AHR was increased in women who have had pre-eclampsia. This association and its possible mechanisms warrant further investigation.

We have followed throughout time the development of allergic airway disease (AAD) in both uninfected mice and mice infected intranasally with murine cytomegalovirus (MCMV). Histological evaluation of lung tissue from uninfected mice with AAD demonstrated mucus plugging after 14 and 21 days of ovalbumin-aerosol challenge, with resolution of mucus plugging occurring by 42 days. In MCMV/AAD mice, mucus plugging was observed after 7 days of ovalbumin-aerosol challenge and remained present at 42 days. The level of interleukin-13 in bronchoalveolar lavage fluid from MCMV/AAD mice was decreased compared with AAD mice and was accompanied by increased levels of interferon-gamma. Levels of Muc5A/C, Muc5B, or Muc2 mucin mRNA in the lungs of MCMV/AAD mice were not elevated compared with AAD mice. MCMV was able to infect the airway epithelium, resulting in decreased expression of Foxj1, a transcription factor critical for ciliogenesis, and a loss of ciliated epithelial cells. In addition, an increase in the number of epithelial cells staining positive for periodic acid-Schiff was observed in MCMV/AAD airways. Together, these findings suggest that MCMV infection of the airway epithelium enhances goblet cell metaplasia and diminishes efficient mucociliary clearance in mice with AAD, resulting in increased mucus plugging.

A 35-year-old woman with a history of atopic diathesis presented to the emergency department with 2 weeks of widespread facial vesiculopustules and eroded vesicles. HSV-1 was found on viral culture and direct fluorescent antibody testing. She was diagnosed with eczema herpeticum, an uncommon and potentially life-threatening viral infection that arises in areas of pre-existing dermatosis. Antiviral treatment for eczema herpeticum is very effective, and should be instituted without delay to avoid significant morbidity and mortality.

Background: The purpose of the present retrospective study was to investigate the association of school-age asthma with acute-bronchiolitis and examine the influence of potential risk factors., Methods: One hundred and eighty-nine children aged 7.5 +/- 2.2 years consecutively hospitalized for respiratory syncytial virus (RSV)-positive acute bronchiolitis during infancy were evaluated by clinical examination and measurement of peak expiratory flow (PEFR), spirometry, IgE and skin-prick testing. Their pulmonary function was compared with that of 60 non-asthmatic matched controls., Results: Of the entire cohort 57.1% were diagnosed as asthmatic. PEFR, the 1-second forced expiratory volume and forced expiratory flow of 50% vital capacity of children with a history of acute bronchiolitis were statistically significantly lower than in the control group (all P < 0.001). All the aforementioned measurements of children with/without asthma were also significantly lower than controls, while values of asthmatics were significantly lower than those of non-asthmatics. The incidence of asthma in childhood was independently associated with breast-feeding <3 months (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI]: 3.1-22.4), at least one positive skin prick test (aOR, 7.1; 95%CI: 2.8-18.1), male gender (aOR, 5.0; 95%CI: 2.2-11.5), evidence of moisture in the home environment (aOR, 2.9; 95%CI: 1.3-6.3) and presence of more than one house-resident smoking indoors (aOR, 4.9; 95%CI: 1.8-9.2)., Conclusion: Children with a history of RSV-bronchiolitis during infancy have an increased risk for developing asthma in childhood, which was independently associated with male gender, breast-feeding <3 months, living in a home environment with moisture damage and/or tobacco smoke by two or more residents and sensitization to at least one aeroallergen. Children with a history of RSV bronchiolitis in infancy had lower spirometry in comparison to matched control group. The difference was more marked for asthmatic ones but remained significant even for non-asthmatic children.

Background: Years after removal from exposure, workers with occupational asthma still show respiratory symptoms and airway hyperresponsiveness on re-exposure to the offending agent., Objective: We investigated the persistence of the respiratory responsiveness to toluene diisocyanate (TDI) in a mouse model., Methods: BALB/C mice received dermal applications of TDI on days 1 and 8, and a single intranasal instillation of TDI on day 10, 15, 20, 25, 30, 40, 50, 60, or 90. After instillation, early (1 hour) changes in ventilatory function and methacholine responsiveness (22 hours) were assessed. Cell counts and macrophage inflammatory protein 2 were measured in bronchoalveolar lavage. Total serum IgE, IgG(1), and IgG(2a) were quantified. Lymphocyte subpopulations were assessed in auricular and cervical lymph nodes, and release of IL-4 and IFN-gamma by these lymph node cells was measured., Results: Toluene diisocyanate-treated mice showed immediate ventilatory changes, increased methacholine reactivity, and an influx of neutrophils and macrophage inflammatory protein 2 in bronchoalveolar lavage as long as 50 days after initial treatment. These mice also showed a relative increase in CD19(+) cells and a decrease in CD4(+) and CD8(+) cells in auricular lymph nodes. Increased release of IL-4 and IFN-gamma in auricular lymph node cells was observed only until 20 days after sensitization. Total serum IgE, IgG(1), and IgG(2a) remained significantly elevated in TDI-sensitized mice until 90 days after dermal sensitization., Conclusion: Ventilatory and lung inflammatory responses decrease with increasing delay between sensitization and challenge, despite persistent humoral signs of sensitization.

Objective: Nasal polyposis is a chronic inflammatory disease of the nasal mucosa. The pathogenesis of nasal polyps is still not entirely known and has been debated for many years. The aim of the present study was to evaluate the expression of interferon gamma and TNF-alpha secreted by Th1 lymphocytes and to analyze their role in the etiology of nasal polyps., Methods: 12 patients with nasal polyposis were selected - 6 of them allergic and 6 non-allergic. Patients with allergy were distinguished from those without allergy on the basis of positive allergy skin tests to dust and serum levels of IgE. Blood sample was obtained from patients and examined for the expression of IFN-gamma and TNF-alpha by intracellular staining procedure after stimulation with PMA/ionomycin and allergen., Results: Negative correlation was found between expression of IFN-gamma and TNF-alpha after PMA/ionomycin stimulation and allergen stimulation (p > 0,05). Statistical analysis of two groups of patients demonstrated that no significant differences in the cytokine expression in allergic versus non-allergic patients were observed although mean value of IFN-gamma and TNF-alpha were lower in allergic patients in comparison to non-allergic (p > 0,05). We didn't observed any correlation between expression of INF-gamma and TNF-alpha and: coexistence of bronchial asthma, allergy to aspirin and local corticosteroid treatment. In patients with recurrent polyposis the expression of INF-gamma was significantly lower (p = 0,05)., Conclusion: This research suggests that IFN-gamma and TNF-alpha play a role in the pathogenesis of nasal polyps but the allergic mechanism may not play a fundamental role in this process. It needs further investigations.

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms. AR was evaluated by performing a novel dosimetric methacholine challenge test. Increased AR to methacholine, defined as a methacholine dose of < or =0.90 mg producing a 40% fall (PD(40)) in the maximal flow at functional residual capacity (V'(max,FRC)), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3-13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5-428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1-22.5), functional residual capacity z-score > or =2 (OR 36.8; 95% CI 2.9-472.6), and V'(max,FRC) z-score (OR 0.5; 95% CI 0.2-0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD(40) V'(max,FRC) >0.90 mg). In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.

Stimulation of mechanoceptors is considered to be the major mechanism of cough. Our aim in this study was to evaluate the relationship between in vivo and in vitro airway reactivity (AR) in chemically- and antigen-induced airway hyperresponsiveness (AHR). AHR was induced chemically (toluene vapors) or via antigen (ovalbumin) in healthy guinea pigs. While toluene inhalation did not cause a significant difference in the number of cough efforts during citric acid nebulization, a significant increase in specific airway resistance after inhalation of histamine was observed, as measured in double chamber body plethysmograph. In contrast, ovalbumin led to a significant increase in both the number of cough efforts and in vivo AR. The in vitro tests confirmed the presence of increased reactivity of tracheal and lung tissue strips to histamine. However, no clear correlation between bronchoconstriction and cough reflex was found in the experimental model used for this study.

Background: The percentage of asthma cases attributable to atopy is the subject of debate., Objectives: The objectives were to estimate the percentage of asthma cases in the US population attributable to atopy and to examine associations between allergen-specific skin tests and asthma., Methods: Data were obtained from the Third National Health and Nutrition Examination Survey, in which subjects age 6 to 59 years were skin tested with 10 allergens. Atopy was defined as at least 1 positive allergen-specific test. Doctor-diagnosed current asthma was assessed by questionnaire., Results: In the United States, 56.3% of the asthma cases were attributable to atopy, and that percentage was greater among males than females, among persons in the highest education category than in lower education categories, and among persons living in highly populated metropolitan areas than in all other areas. Each allergen-specific test was strongly associated with asthma before adjustment (odds ratios varied from 2.1 to 4.5); however, after adjustment by all the allergens, only tests to cat, Alternaria, white oak, and perennial rye were independently associated with asthma. Perennial rye was inversely associated with asthma. Of the 10 allergens, a positive response to cat accounted for the highest percentage of asthma cases (29.3%)., Conclusion: About half of the current asthma cases in the US population represented by the Third National Health and Nutrition Examination Survey were attributable to atopy. Some allergen-specific skin tests were not independently associated with asthma., Clinical Implications: If atopy could be prevented or reversed, or its effect on asthma blocked, then a large percentage of asthma cases in the US population could be prevented.

Objectives: This study investigated the clinical impression that there was an increased prevalence of respiratory disorders in both the Hypermobility Syndrome (HMS)/Benign Joint Hypermobility Syndrome (BJHS) and Ehlers-Danlos Syndrome (EDS), compared with the normal population., Methods: A questionnaire was distributed to 509 subjects (221 healthy controls, 126 HMS, 162 EDS) who documented respiratory symptoms and previously diagnosed respiratory and atopic disorders. A subgroup of 157 responders underwent full clinical and serological assessments, and 57 subjects were assessed physiologically., Results: A significant increase in the frequency of a wide range of respiratory symptoms and reduced exercise tolerance was observed in subjects with both HMS and EDS compared with controls. In particular, there was an increased prevalence of asthmatic symptoms (HMS: OR 2.4, 95% CI 1.4-4.1, p = 0.002; EDS: OR 3.1, 95% CI 1.8-5.2, p<0.001) and atopy (HMS: OR 2.7, 95% CI 1.6-4.5, p<0.001; EDS: OR 2.6, 95% CI 1.6-4.4, p<0.001), which was subsequently confirmed by clinical assessment. Pulmonary physiological studies revealed increased lung volumes, impaired gas exchange and an increased tendency of both the lower and upper airways to collapse., Conclusions: We have demonstrated, for the first time, that individuals with HMS/BJHS and EDS have respiratory symptoms in association with various pulmonary physiological abnormalities. The increased prevalence of asthma may be due to linkage disequilibrium between the genes causing these conditions or a function of the connective tissue defect itself. In the non-asthmatic population, changes in the mechanical properties of the bronchial airways and lung parenchyma may underlie the observed increased tendency of the airways to collapse.