Allergic Exacerbation Research Articles

Pattern of aeroallergen sensitivity in bronchial asthma patients: A cross-sectional study in a tertiary care centre

Abstract INTRODUCTION: Asthma is one of the most common chronic noncommunicable diseases. Aeroallergens are often implicated in the pathogenesis of allergic rhinitis (AR) and bronchial asthma (BA). Identification of the most prevalent aeroallergens, to which the patients are sensitized, plays an important role in the diagnosis and treatment of BA. Among various diagnostic tests for detecting sensitizing allergens, the skin prick test (SPT) is a useful method to demonstrate hypersensitivity to a specific antigen. METHODOLOGY: This was a hospital-based cross-sectional observational study carried out on BA patients attending our institute during the year 2020–2021. BA patients of both sex and age between 18 and 65 years, diagnosed according to the latest GINA guidelines and gave written informed consent were included in the study. After recruitment, the participant’s detailed medical history and sociodemographic data were obtained. Total eosinophil count (TEC), serum immunoglobulin E (S. IgE), X-ray PNS, chest X-ray, and other investigations as required were done. SPT was done using 63 antigens, which included 20 pollens, 8 fungi, 5 insects, 8 dusts, 4 dander, 2 dust mites, 2 feathers, and 14 food allergens. RESULTS: Six thousand and three hundred SPTs were performed with a total of 63 allergens using the modified SPT technique. Of the 100 patients enrolled, 71% were diagnosed as BA and 29% as BA with AR. Among the study population, 44% were females and 56% were males. The majority was constituted of young adults, aged 21–30 years. More than half of the patients (68%) had their duration of disease between 1 and 5 years. Seventy percent patients reported seasonal variation in symptoms, and spring season was associated with maximum allergic exacerbations followed by winter. Significant positive reaction (≥2+) in SPT was found in 89% of patients, whereas 11% tested negative for all allergens. pollens were the most common aeroallergen group identified, whereas feathers and food allergens were the least common in the present study. Among pollen, Prosopis juliflora was the most common (24%) pollen-causing sensitization closely followed by Holoptelea integrifolia (17%) and Gynandropsis gynandra (18%). Female cockroach (37%) and mosquito (37%) were the most common insects to which the majority of the population were sensitized. Dermatophagoides farinae was accounting for 23% of positive reactions in the study population. Alternaria tenuis was the most common fungus to which 6% of the patients tested positive. House dust (17%) was the most common dust subgroup associated with positive SPT. Among danders, buffalo dander (8%) was observed to be the most common sensitizer followed by dog dander (6%). The pigeon feather was the most common feather identified. A strong positive correlation was observed between S. IgE and the number of allergens that tested positive (r = 0.489; P < 0.0001) and a strong positive correlation was observed between serum TEC and the number of allergens that tested positive (r = 0.430; P < 0.0001). CONCLUSION: Our study identified pollen as the most common sensitizing aeroallergen followed by insects. Such studies, conducted from time to time, shed light on the changing trends of the commonly prevalent allergens in a particular area. The identification of offending allergens for a patient also explores treatment options such as allergen-specific immunotherapy.

AMPK suppresses Th2 cell responses by repressing mTORC2

Allergic inflammation is a T helper 2 (Th2) cell-driven pathophysiological phenomenon, but the mechanism by which the metabolic cascade affects Th2 cell differentiation remains unclear. In this study, we investigated the roles of AMP-activated protein kinase (AMPK) and intracellular energy sensors in Th2 cell differentiation and the pathogenesis of allergic inflammation. Accordingly, T-cell-specific AMPK or Sirtuin 1 (Sirt1)-knockout mice were subjected to allergic inflammation, and their Th2 cell responses were investigated. The results demonstrated that inducing allergic inflammation in AMPK- and Sirt1-knockout mice increased Th2 cell responses and exacerbated allergic phenotypes. Furthermore, treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, ameliorated allergic inflammation in mice. Mechanistically, our findings revealed that AMPK repressed mechanistic target of rapamycin complex 2 (mTORC2), which downregulated the expression of suppressor of cytokine signaling 5 (SOCS5) in CD4+ T cells. In addition, the loss of AMPK signaling reduced SOCS5 expression and increased interleukin-4-STAT6–GATA3 axis-mediated Th2 cell differentiation. Finally, the T-cell-specific deletion of Rictor, a member of mTORC2, in Sirt1T-KO mice led to the reversal of allergic exacerbation to the level in control mice. Overall, our findings suggest that AMPK in CD4+ T cells inhibits the differentiation of Th2 cells by repressing mTORC2 and thus serves as a potential target for Th2 cell-associated diseases.

Segmental Bronchial Allergen Challenge Elicits Distinct Metabolic Phenotypes in Allergic Asthma

Asthma is a complex syndrome associated with episodic decompensations provoked by aeroallergen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately inform biomarker-driven therapy. A better understanding of the pathophysiological pathways driving allergic exacerbations is needed. We hypothesized that disease-associated pathways could be identified in humans by unbiased metabolomics of bronchoalveolar fluid (BALF) during the peak inflammatory response provoked by a bronchial allergen challenge. We analyzed BALF metabolites in samples from 12 volunteers who underwent segmental bronchial antigen provocation (SBP-Ag). Metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS) followed by pathway analysis and correlation with airway inflammation. SBP-Ag induced statistically significant changes in 549 features that mapped to 72 uniquely identified metabolites. From these features, two distinct inducible metabolic phenotypes were identified by the principal component analysis, partitioning around medoids (PAM) and k-means clustering. Ten index metabolites were identified that informed the presence of asthma-relevant pathways, including unsaturated fatty acid production/metabolism, mitochondrial beta oxidation of unsaturated fatty acid, and bile acid metabolism. Pathways were validated using proteomics in eosinophils. A segmental bronchial allergen challenge induces distinct metabolic responses in humans, providing insight into pathogenic and protective endotypes in allergic asthma.

Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation

BackgroundRespiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation.MethodsSensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry.ResultsWhile thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well.ConclusionsTaken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.

IL-9 regulates type-2 CD4 tissue resident memory cell mediated allergic airway recall responses

Abstract Allergic asthma is a chronic inflammatory lung disease with intermittent flares where patients experience symptoms mediated by memory T cells. Allergen-specific CD4+ tissue resistant memory (Trm) cells in peripheral tissues have been reported to facilitate mucosal barrier immunity. However, the precise role of Trm CD4+ T cells in allergic exacerbations is not clearly defined. In this study we identified interleukin-9 (IL-9)-secreting allergen-specific CD4 T cells with a memory phenotype that regulate recall response to Aspergillus fumigatus. Inhibition of circulating T cells by administering FTY720 in the last month of rest, diminished the total CD4 T cells population in the lung, while the IL-9 secreting CD4 tissue resident cells remained stable. Single-cell RNA-seq and ATAC-seq confirmed the presence of multi-cytokine producing IL-9 secreting CD4 Trms in early recall responses to the allergen. Blockade of IL-9 prior to recall challenge phase reduced overall allergic lung inflammation observed through both flow-cytometry and single cell-RNA-seq analysis. IL-9 neutralization reduced cellularity of several populations in the lung including granulocytes and lymphocytes. Moreover, the expression of genes associated with mucus metaplasia including Muc2, Muc5ac, Muc5b, and Bpifb1 were significantly reduced in type-2 alveolar and epithelial cells with anti-IL-9 treatment. These findings demonstrate that IL-9-producing Trms play an important role in mediating allergic memory responses. IL-9 could be a promising therapeutic target specifically in patients showing symptoms of intermittent allergic response.

A single cell approach to identify the role of IL-9 secreting tissue-resident CD4+ T cells in allergic airway recall responses

Abstract Allergic asthma is a chronic intermittent inflammatory lung disease where patients experience relatively few symptoms between exacerbations precipitated by allergen-challenge of allergic memory responses. Allergen-specific CD4+ T cells are believed to be a major mediator of allergic memory responses through the production of type 2 cytokines including IL-4, IL-5, IL-13 and IL-9. Recently, tissue-resident memory (Trm) cells have been identified in peripheral tissues that mediate mucosal barrier immunity. However, the precise role of Trm CD4+ T cells in allergic exacerbations is not clearly defined. In studies to examine the role of IL-9 in allergen-specific Trm responses to Aspergillus fumigatus we observed that all IL-9-secreting T cells had a resident memory phenotype. Inhibition of circulating T cells by administering FTY720 in the last month of rest, diminished the total CD4 T cells population in the lung, while the Th9 cells remained stable. Blockade of IL-9 prior to recall challenge phase reduced overall allergic lung inflammation as assessed both by flow cytometry and single cell RNA-seq. Within eight hours after challenge, IL-9 is one of the top genes identified by scRNA-seq that distinguishes ST2+ and ST2− CD4+ T cell populations in the lung. Using IL-9-reporter mice we also compared gene expression in isolated IL-9+ T cells and other type 2 T cells. These findings demonstrate that IL-9-producing Trms play an important role in mediating allergic memory responses. IL-9 could be a promising therapeutic target specifically in patients showing symptoms of intermittent allergic response.

Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease

Many studies have linked severe RSV infection during early-life with an enhanced likelihood of developing childhood asthma, showing a greater susceptibility in boys. Our studies show that early-life RSV infection leads to differential long-term effects based upon the sex of the neonate; leaving male mice prone to exacerbation upon secondary allergen exposure while overall protecting female mice. During initial viral infection, we observed better viral control in the female mice with correlative expression of interferon-β that was not observed in male mice. Additionally, we observed persistent immune alterations in male mice at 4 weeks post infection. These alterations include Th2 and Th17-skewing, innate cytokine expression (Tslp and Il33), and infiltration of innate immune cells (DC and ILC2). Upon exposure to allergen, beginning at 4 weeks following early-life RSV-infection, male mice show severe allergic exacerbation while female mice appear to be protected. Due to persistent expression of TSLP following early-life RSV infection in male mice, genetically modified TSLPR−/− mice were evaluated and demonstrated an abrogation of allergen exacerbation in male mice. These data indicate that TSLP is involved in the altered immune environment following neonatal RSV-infection that leads to more severe responses in males during allergy exposure, later in life. Thus, TSLP may be a clinically relevant therapeutic target early in life.

Epithelial cell-derived cytokines: more than just signaling the alarm.

The epithelial cell-derived cytokines thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 are central regulators of type 2 immunity, which drives a broad array of allergic responses. Often characterized as "alarmins" that are released by the barrier epithelium in response to external insults, these epithelial cell-derived cytokines were initially thought to act only early in allergic inflammation. Indeed, TSLP can condition dendritic cells to initiate type 2 responses, and IL-33 may influence susceptibility to asthma through its role in establishing the immune environment in the perinatal lungs. However, TSLP, IL-33, and IL-25 all regulate a broad spectrum of innate immune cell populations and are particularly potent in eliciting and activating type 2 innate lymphoid cells (ILC2s) that may act throughout allergic inflammation. Recent data suggest that a TSLP/ILC axis may mediate steroid resistance in asthma. Recent identification of memory Th2 cell subsets that are characterized by high receptor expression for TSLP, IL-33, and IL-25 further supports a role for these cytokines in allergic exacerbations. There is therefore growing interest in developing biologics that target TSLP, IL-33, and IL-25. This Review provides an overview of TSLP, IL-33, and IL-25 and the development of blocking antibodies that target these epithelial cell-derived cytokines.

Anisakiasis in Italy: Analysis of hospital discharge records in the years 2005-2015.

BackgroundAnisakiasis is a fish-borne zoonosis caused by the ingestion of marine food infected with Anisakis third-stage larvae, widespread marine parasitic nematodes. Gastrointestinal and/or allergic clinical signs and symptoms are not specific. While frequently reported in countries with large raw fish consumption as Japan, the global prevalence of anisakiasis may be severely underestimated due to limitations of available diagnostic tools and to diverse clinical manifestations. Recently, infective larvae were found in the same localization with gastrointestinal tumors. The occurrence of allergic exacerbation upon secondary exposure and the possible occupational exposure, highlight the need to increase scientific evidences on anisakiasis.MethodsWe performed a retrospective descriptive study using analysis of Hospital Discharge Records (HDRs) from 2005 to 2015 in Italy, with particular attention to allergic manifestations. Descriptive statistics and multivariate analyses were performed using backward step-wise logistic regression models to assess spatial distribution and temporal trend as well as the variables independently associated with the allergic clinical signs and symptoms in Italian cases of anisakiasis.ResultsHDRs reporting the ICD-9 code for anisakiasis were retrieved (370), with a higher number of cases reported from central and southern regions, with particular regard to populations inhabiting the coastal territories. Around 40% of patients presented allergic manifestations and half of them showed serious allergic reactions. The multivariate analyses showed an independent association between allergic manifestations and features as living in southern regions and female gender, while anaphylactic episodes was independently associated only with female gender.ConclusionThe present study is the first attempt to a better understanding of the epidemiological picture of anisakiasis in Italy, mining official data. A common strategy on data collection, monitoring and reporting would favor a more accurate epidemiological scenario in Italy, since the report of the diseases is not mandatory.

Effect modification of ambient air pollution in the associations between aeroallergens and allergic disease medication relievers in Ontario, Canada

Background: Ambient air pollution may modify the effect of aeroallergens on allergic diseases through enhanced inflammatory processes. However, further evidence is needed in order to clarify this effect modification influence. Aims: Investigate the effect modifying influence of outdoor air pollution in the associations between daily levels of ambient aeroallergens and daily numbers of medications sold to relieve allergic diseases such as asthma, allergic rhinitis and conjunctivitis. Methods: This study uses a multi-city time series approach by including seven cities in the province of Ontario, Canada. In each city, daily levels of aeroallergens (tree, pollen, mold) taken from fixed site monitoring stations from years 2007 to 2011 were obtained. Daily numbers of prescription and over-the-counter (OTC) medication sales used to relieve symptoms of asthma, allergic rhinitis and conjunctivitis were also obtained for the same time period for each city. A distributed lag Poisson regression model adjusted for seasonal trends, day-of-the-week, temperature and relative humidity was used by including interaction terms between aeroallergen levels and a dichotomized variable (low/high) characterizing levels of specific air pollutants (NO2, PM2.5, CO, O3 and SO2). Results were pooled across all cities using random effects model. Results: The relative risks characterizing the associations between daily pollen levels and daily medication reliever sales for asthma and allergic rhinitis were stronger on days with elevated levels of PM2.5 compared to days with lower levels (P value for interaction < 0.05). Relative risks (95% confidence interval) for an interquartile increase in tree pollen levels ranged from 1.15 to 1.30 on days of high PM2.5 levels. Conclusions: Results of this study suggest that ambient air pollution enhance the effect of pollen on asthma and allergic rhinitis. A reduction in ambient air pollution levels could reduce allergic exacerbations of asthma and allergic rhinitis.

Advances in pediatric asthma in 2012: Moving toward asthma prevention

Last year's "Advances in pediatric asthma: moving forward" concluded the following: "Now is also the time to utilize information recorded in electronic medical records to develop innovative disease management plans that will track asthma over time and enable timely decisions on interventions in order to maintain control that can lead to disease remission and prevention." This year's summary will focus on recent advances in pediatric asthma on modifying disease activity, preventing asthma exacerbations, managing severe asthma, and risk factors for predicting and managing early asthma, as indicated in Journal of Allergy and Clinical Immunology publications in 2012. Recent reports continue to shed light on methods to improve asthma management through steps to assess disease activity, tools to standardize outcome measures in asthma, genetic markers that predict risk for asthma and appropriate treatment, and interventions that alter the early presentation of asthma to prevent progression. We are well on our way to creating a pathway around wellness in asthma care and also to use new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.

Does air pollution increase the effect of aeroallergens on hospitalization for asthma?

Clinical experiments demonstrate that the asthmatic response to an aeroallergen can be enhanced by prior exposure to an air pollutant. We sought to compare the effects of ambient aeroallergens on hospitalization for asthma between high and low air pollution days in 11 large Canadian cities. Daily time-series analysis was used, and results were adjusted for day of the week, temperature, barometric pressure, and relative humidity. The relative risk of admission for an interquartile increase in tree pollen levels was 1.124 (95% CI, 1.101-1.147) on days of lower values of fine particulate matter with a median aerodynamic diameter less than or equal to 2.5 μm (PM(2.5)) compared with 1.179 (95% CI, 1.149-1.21) on days of higher PM(2.5) values. Significant (P ≤ .05) differences in the relative risks of admission between lower versus higher values of particulate matter with a median aerodynamic diameter less than or equal to 10 μm in diameter were 1.149 (95% CI, 1.118-1.181) versus 1.210 (95% CI, 1.161-1.261) for ascomycetes, 1.112 (95% CI, 1.085-1.14) versus 1.302 (95% CI, 1.242-1.364) for basidiomycetes, 1.159 (95% CI, 1.125-1.195) versus 1.149 (95% CI, 1.129-1.169) for deuteromycetes, and 1.061 (95% CI, 1.016-1.107) versus 1.117 (95% CI, 1.092-1.143) for weeds. We identified an association between aeroallergens and hospitalizations for asthma, which was enhanced on days of higher air pollution. Minimizing exposure to air pollution might reduce allergic exacerbations of asthma.

Double-Stranded RNA Exacerbates Pulmonary Allergic Reaction through TLR3: Implication of Airway Epithelium and Dendritic Cells

Respiratory viral infections have been implicated in exacerbations of allergic asthma, characterized by a Th2-biased immune response. Respiratory viruses target airway epithelial cells and dendritic cells (DCs). Their activation is, at least in part, mediated by the TLR3-dependent recognition of virus-derived dsRNA. To elucidate the role of epithelial cells and DCs and the implication of TLR3/Toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) pathway, we developed a mouse model of lung allergic exacerbation. The effect of intranasal administration of dsRNA in OVA-sensitized wild-type mice and TRIF(-/-) mice was evaluated on airway hyperresponsiveness and pulmonary inflammation. Our data demonstrated that treatment with dsRNA significantly increased the airway hyperresponsiveness, the lung inflammation, and the OVA-specific Th2 response. This was associated with an infiltrate of eosinophils, myeloid DCs, and T lymphocytes. TRIF activation was required for the development of dsRNA-induced exacerbation of the allergic reaction. Intratracheal transfer of IL-4/dsRNA/OVA-pretreated DCs also triggered exacerbation of the allergic reaction, whereas cells primed with dsRNA/OVA had a more limited effect. dsRNA-induced production of CCL20 by airway epithelium was associated with DC recruitment. In vivo and in vitro treatment with dsRNA amplified airway epithelial production of the pro-Th2 chemokines CCL11 and CCL17, their secretion being enhanced by Th2 cytokines. In conclusion, dsRNA derived from respiratory viruses trigger exacerbation of the pulmonary allergic reaction through TLR3/TRIF-dependent pathway. Moreover, Th2 cytokines participate in this process by modulating the response of airway epithelium and DCs to dsRNA.

TLR3 in Human Eosinophils: Functional Effects and Decreased Expression during Allergic Rhinitis

Background/Aim: Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils. Methods: BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved. Results: TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-ĸB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release. Conclusions: Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.

Role of atopic status in Toll-like receptor (TLR)7- and TLR9-mediated activation of human eosinophils

Viral respiratory infections are increasingly implicated in allergic exacerbations. The mechanisms behind this are not known, but a virus-induced activation of eosinophils through TLRs could be involved. Herein, we investigated the expression and function of TLR7 and TLR9 in purified eosinophils from peripheral blood and assessed their role in allergic airway inflammation. Eosinophils expressed TLR7 and TLR9 proteins. Stimulation with the cognate ligands R-837 and CpG was found to prolong survival, up-regulate expression of CD11b and conversely down-regulate L-selectin expression, increase expression of the activation marker CD69, facilitate the chemotactic migration, and enhance IL-8 secretion by eosinophils. Also, CpG induced release of eosinophil-derived neurotoxin (EDN), and R-837 failed to do so. Analogously, eosinophils activated by CpG, but not R-837, promoted airway epithelial cell death and cytokine release. Priming with the allergic mediators histamine, IL-4, and most prominently IL-5, augmented the TLR-induced IL-8 and EDN secretion, revealing an ability to sensitize eosinophils for TLR7 and TLR9 activation. Moreover, the TLR responses of eosinophils were higher in allergic as compared with healthy subjects, manifested by an increase in IL-8 and EDN release. Correspondingly, allergic subjects displayed an elevated serum level of IL-5, suggesting increased IL-5-mediated priming. This study shows that activation via TLR7 and TLR9 affects several eosinophil functions and that the atopic status of the donor and the presence of a Th2-like cytokine milieu affect the outcome of the response. Thus, eosinophil activation via TLR7 and TLR9 might engender a link between viral infection and allergic exacerbations.

Comparison of expression profiles induced by dust mite in airway epithelia reveals a common pathway

Airway epithelial cells have shown to be active participants in the defense against pathogens by producing signaling and other regulatory molecules in response to the encounter. In previous manuscripts, we have studied the effect of house dust mite (HDM) extract on both an epithelial cell-line (H292) and primary nasal epithelial cell. When we compare these responses we conclude that the H292 cells more closely resemble nasal epithelium of healthy controls (share 107 probe-sets) than of allergic individuals (share 17 probe-sets). Interestingly, probably because of an absent intraindividual variation between samples, more probe-sets (8280) change expression significantly in H292 than in either healthy (555) or allergic (401) epithelium. A direct comparison of all the responses in these epithelial cells reveals a core-response to HDM of just 29 genes. These genes (CCL20, IL-8, CXCL2, CXCL1, IL-1B, AREG, TNFAIP3, HBEGF, PTGS2, BMP2, LDLR, PLAUR, PLAU, NFKB2, NFKB1, JUN, ATF3, EGR1, NPC1, TICAM1, EPHA2, CTGF, DUSP1, SPRY1, TLR-3, complement factor C3, IVNS1ABP, SerpinB3, and PSAT1) have described links with allergy or inflammation and may even describe the well-established relationship between viral infections and allergic exacerbations or allergy development.

Quantitative sputum gram stains in chronic bronchial disease.

The assessment of bacterial flora of the bronchial system can provide useful information for determining the presence of acute bacterial infections in patients with chronic bronchial disease. The authors examined the value of quantitative sputum gram stains performed in patients during acute bronchial exacerbations, recovery from such exacerbations, acute allergic exacerbations of chronic extrinsic asthma, and a stable period. The mean number of each morphologic type of microorganism was determined for 20 oil immersion fields. Ninety-nine percent of the patients without clinical evidence of bacterial infection had fewer than 16Haemophilus influenzae-like, 10 pneumococcus-like, and 18Neisseria-like microorganisms per gram stain oil immersion field. Even during the recovery period, when the patients were on antibiotics, we noted few gram negative rods, diphtheroid-like, or staphylococcus-like microorganisms on gram stain. The data indicate that upper limits may be set for numbers of microorganisms seen on gram stain in the absence of clinically apparent acute bacterial infection in chronic lung disease.