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Sample records for allergic lung diseases

  1. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome.

    PubMed

    Eyring, Kenneth R; Pedersen, Brent S; Yang, Ivana V; Schwartz, David A

    2015-01-01

    Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease. PMID:26642056

  2. Necessary and sufficient role for T helper cells to prevent fungal dissemination in allergic lung disease.

    PubMed

    Porter, Paul C; Roberts, Luz; Fields, Anna; Knight, Morgan; Qian, Yuping; Delclos, George L; Han, Shuhua; Kheradmand, Farrah; Corry, David B

    2011-11-01

    Mucosal immune responses to fungal infection range from T helper type 2 (Th2) cell-directed allergic inflammation to Th1-predominant neutrophilic inflammation, but the mechanisms directing these divergent mucosal immune outcomes and the role of T cells in host defense against mucosal fungal infections are not known. Here we examined the mouse mucosal immune responses to 12 filamentous environmental fungal species over a broad range of exposure doses and determined the requirement of T cells for host defense. For all tested fungi, low-grade conidium exposures induced Th2- and eosinophil-predominant allergic lung disease, whereas higher exposures led to rapid conversion to neutrophil- and Th1 cell-predominant inflammation, a phenomenon we term immune phenotype switching. All fungal exposure doses were further linked to the secretion of interleukin-17A (IL-17A). Fungal infections with Curvularia lunata and Aspergillus fumigatus were typically confined to the airway during allergic inflammation but became locally invasive and disseminated to the brain at higher conidium challenge doses, in association with predominant Th1 responses. Fungal dissemination occurred at relatively low challenge doses with the conidia of Aspergillus fumigatus administered to recombinase activating gene 1 (Rag-1)-deficient mice, which lack B and T cells, but B cell-deficient μMT mice and T helper cell-reconstituted Rag-1-deficient mice were comparable to wild-type mice in preventing fungal dissemination. Our findings demonstrate that Th2 cell-predominant allergic responses followed by immune phenotype switching and fungal dissemination are highly predictable outcomes with progressive fungal infectious burdens and that T helper cell responses are protective against lethal fungal dissemination.

  3. Epigenomics and allergic disease.

    PubMed

    Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

    2013-12-01

    Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment.

  4. Epigenomics and allergic disease

    PubMed Central

    Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

    2014-01-01

    Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment. PMID:24283882

  5. Genetics of Allergic Diseases

    PubMed Central

    Ortiz, Romina A.; Barnes, Kathleen C.

    2015-01-01

    The allergic diseases are complex phenotypes for which a strong genetic basis has been firmly established. Genome-wide association studies (GWAS) has been widely employed in the field of allergic disease, and to date significant associations have been published for nearly 100 asthma genes/loci, in addition to multiple genes/loci for AD, AR and IgE levels, for which the overwhelming number of candidates are novel and have given a new appreciation for the role of innate as well as adaptive immune-response genes in allergic disease. A major outcome of GWAS in allergic disease has been the formation of national and international collaborations leading to consortia meta-analyses, and an appreciation for the specificity of genetic associations to sub-phenotypes of allergic disease. Molecular genetics has undergone a technological revolution, leading to next generation sequencing (NGS) strategies that are increasingly employed to hone in on the causal variants associated with allergic diseases. Unmet needs in the field include the inclusion of ethnically and racially diverse cohorts, and strategies for managing ‘big data’ that is an outcome of technological advances such as sequencing. PMID:25459575

  6. Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease.

    PubMed

    Foong, Rachel E; Bosco, Anthony; Troy, Niamh M; Gorman, Shelley; Hart, Prue H; Kicic, Anthony; Zosky, Graeme R

    2016-09-01

    Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.

  7. Lung disease

    MedlinePlus

    ... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...

  8. Therapeutic strategies for allergic diseases

    NASA Astrophysics Data System (ADS)

    Barnes, Peter J.

    1999-11-01

    Many drugs are now in development for the treatment of atopic diseases, including asthma, allergic rhinitis and atopic dermatitis. These treatments are based on improvements in existing therapies or on a better understanding of the cellular and molecular mechanisms involved in atopic diseases. Although most attention has been focused on asthma, treatments that inhibit the atopic disease process would have application to all atopic diseases, as they often coincide. Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments.

  9. Asthma and Respiratory Allergic Disease

    EPA Science Inventory

    The pathogenesis of non-communicable diseases such as allergy is complex and poorly understood. The causes of chronic allergic diseases including asthma involve to a large extent, immunomodulation of the adaptive and particularly the innate immune systems and are markedly influen...

  10. Allergic diseases in the elderly

    PubMed Central

    2011-01-01

    Demographic distribution of the population is progressively changing with the proportion of elderly persons increasing in most societies. This entails that there is a need to evaluate the impact of common diseases, such as asthma and other allergic conditions, in this age segment. Frailty, comorbidities and polymedication are some of the factors that condition management in geriatric patients. The objective of this review is to highlight the characteristics of allergic diseases in older age groups, from the influence of immunosenescence, to particular clinical implications and management issues, such as drug interactions or age-related side effects. PMID:22409889

  11. Climate change and allergic disease.

    PubMed

    Shea, Katherine M; Truckner, Robert T; Weber, Richard W; Peden, David B

    2008-09-01

    Climate change is potentially the largest global threat to human health ever encountered. The earth is warming, the warming is accelerating, and human actions are largely responsible. If current emissions and land use trends continue unchecked, the next generations will face more injury, disease, and death related to natural disasters and heat waves, higher rates of climate-related infections, and wide-spread malnutrition, as well as more allergic and air pollution-related morbidity and mortality. This review highlights links between global climate change and anticipated increases in prevalence and severity of asthma and related allergic disease mediated through worsening ambient air pollution and altered local and regional pollen production. The pattern of change will vary regionally depending on latitude, altitude, rainfall and storms, land-use patterns, urbanization, transportation, and energy production. The magnitude of climate change and related increases in allergic disease will be affected by how aggressively greenhouse gas mitigation strategies are pursued, but at best an average warming of 1 to 2 degrees C is certain this century. Thus, anticipation of a higher allergic disease burden will affect clinical practice as well as public health planning. A number of practical primary and secondary prevention strategies are suggested at the end of the review to assist in meeting this unprecedented public health challenge.

  12. ALLERGIC DISEASES AND ASTHMA IN ADOLESCENTS.

    PubMed

    Adamia, N; Jorjoliani, L; Khachapuridze, D; Katamadze, N; Chkuaseli, N

    2015-06-01

    The goal of our research was to find out, whether asthma phenotyping, based on presence of accompanying allergic diseases is significant for asthma classification or not. Research was conducted on the basis of questioning of random and representative cohorts of Tbilisi children's population, by cross-section method of epidemiological research. Special extended screening questionnaire was developed for epidemiological study of allergic diseases. Diagnostic criterion for allergy was analyzed and representative cohort was selected. Research was conducted in 2010-2014 period. Studied population included 1450 children from 2 to 17 years age representing Tbilisi general population (of them, 850 girls and 600 boys). As a result of research the following findings were made: asthma was confirmed where at least two of the listed was present: diagnosis of asthma made by doctor, asthma symptoms and consumption of drugs against asthma. Allergic rhinitis was confirmed, where more than one of the listed symptoms was present and children should not have caught cold, rhinorrhea, nasal obstruction or snore, combined or IgE with some inhalation allergen. Atopic dermatitis was confirmed if the subject had atopic dermatitis at a time of interview or clinical study. Markers of asthma severity were based on number of asthma episodes and number of symptoms, or regular consumption of corticosteroids, number of missed days at school and answer of subjects to the question: for the past year what was the degree of discomfort attributable to asthma ("very high" - "absolutely not"). Allergic sensitization was assessed based on the skin prick-test and test of specific immunoglobulin E in serum and was deemed positive where the average diameter of blebs in skin prick tests was 3 mm larger than negative control and IgE-0,35kU/l. Lung function was assessed by means of respirometers, by evaluating maximal forced expiration data and flow-volume curves. Allergic rhinitis was regarded as the most

  13. Lung Diseases

    MedlinePlus

    When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...

  14. Air pollution and allergic disease.

    PubMed

    Kim, Haejin; Bernstein, Jonathan A

    2009-03-01

    Over the past several decades, there has been increased awareness of the health effects of air pollution and much debate regarding the role of global warming. The prevalence of asthma and allergic disease has risen in industrialized countries, and most epidemiologic studies focus on possible causalities between air pollution and these conditions. This review examines salient articles and summarizes findings important to the interaction between allergies and air pollution, specifically volatile organic compounds, global warming, particulate pollutants, atopic risk, indoor air pollution, and prenatal exposure. Further work is necessary to determine whether patients predisposed to developing allergic disease may be more susceptible to the health effects of air pollutants due to the direct interaction between IgE-mediated disease and air pollutants. Until we have more definitive answers, patient education about the importance of good indoor air quality in the home and workplace is essential. Health care providers and the general community should also support public policy designed to improve outdoor air quality by developing programs that provide incentives for industry to comply with controlling pollution emissions.

  15. Environmental Changes, Microbiota, and Allergic Diseases

    PubMed Central

    Kim, Byoung-Ju; Lee, So-Yeon; Kim, Hyo-Bin; Lee, Eun

    2014-01-01

    During the last few decades, the prevalence of allergic disease has increased dramatically. The development of allergic diseases has been attributed to complex interactions between environmental factors and genetic factors. Of the many possible environmental factors, most research has focused on the most commonly encountered environmental factors, such as air pollution and environmental microbiota in combination with climate change. There is increasing evidence that such environmental factors play a critical role in the regulation of the immune response that is associated with allergic diseases, especially in genetically susceptible individuals. This review deals with not only these environmental factors and genetic factors but also their interactions in the development of allergic diseases. It will also emphasize the need for early interventions that can prevent the development of allergic diseases in susceptible populations and how these interventions can be identified. PMID:25228995

  16. Allergic disease as an association of steroid sulphatase deficiency.

    PubMed

    Sakura, N; Nishimura, S; Matsumoto, T; Ohsaki, M; Ogata, T

    1997-11-01

    Ten of 31 patients with steroid sulphatase (STS) deficiency were found to have an allergic disease (bronchial asthma, allergic rhinitis, or atopic dermatitis). STS deficiency may predispose patients to allergic disease.

  17. Regulation of allergic lung inflammation by endothelial cell transglutaminase 2.

    PubMed

    Soveg, Frank; Abdala-Valencia, Hiam; Campbell, Jackson; Morales-Nebreda, Luisa; Mutlu, Gökhan M; Cook-Mills, Joan M

    2015-09-15

    Tissue transglutaminase 2 (TG2) is an enzyme with multiple functions, including catalysis of serotonin conjugation to proteins (serotonylation). Previous research indicates that TG2 expression is upregulated in human asthma and in the lung endothelium of ovalbumin (OVA)-challenged mice. It is not known whether endothelial cell TG2 is required for allergic inflammation. Therefore, to determine whether endothelial cell TG2 regulates allergic inflammation, mice with an endothelial cell-specific deletion of TG2 were generated, and these mice were sensitized and challenged in the airways with OVA. Deletion of TG2 in endothelial cells blocked OVA-induced serotonylation in lung endothelial cells, but not lung epithelial cells. Interestingly, deletion of endothelial TG2 reduced allergen-induced increases in respiratory system resistance, number of eosinophils in the bronchoalveolar lavage, and number of eosinophils in the lung tissue. Endothelial cell deletion of TG2 did not alter expression of adhesion molecules, cytokines, or chemokines that regulate leukocyte recruitment, consistent with other studies, demonstrating that deletion of endothelial cell signals does not alter lung cytokines and chemokines during allergic inflammation. Taken together, the data indicate that endothelial cell TG2 is required for allergic inflammation by regulating the recruitment of eosinophils into OVA-challenged lungs. In summary, TG2 functions as a critical signal for allergic lung responses. These data identify potential novel targets for intervention in allergy/asthma.

  18. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  19. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  20. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  1. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  2. 38 CFR 3.380 - Diseases of allergic etiology.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic...

  3. Japanese Guideline for Occupational Allergic Diseases 2014.

    PubMed

    Dobashi, Kunio; Akiyama, Kazuo; Usami, Atsushi; Yokozeki, Hiroo; Ikezawa, Zenro; Tsurikisawa, Naomi; Nakamura, Yoichi; Sato, Kazuhiro; Okumura, Jiro

    2014-09-01

    In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

  4. [Epigenetics in allergic diseases and asthma].

    PubMed

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human. PMID:27055949

  5. [Epigenetics in allergic diseases and asthma].

    PubMed

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human.

  6. Regulatory T cells in allergic diseases.

    PubMed

    Noval Rivas, Magali; Chatila, Talal A

    2016-09-01

    The pathogenesis of allergic diseases entails an ineffective tolerogenic immune response to allergens. Regulatory T (Treg) cells play a key role in sustaining immune tolerance to allergens, yet mechanisms by which Treg cells fail to maintain tolerance in patients with allergic diseases are not well understood. We review current concepts and established mechanisms regarding how Treg cells regulate different components of allergen-triggered immune responses to promote and maintain tolerance. We will also discuss more recent advances that emphasize the "dual" functionality of Treg cells in patients with allergic diseases: how Treg cells are essential in promoting tolerance to allergens but also how a proallergic inflammatory environment can skew Treg cells toward a pathogenic phenotype that aggravates and perpetuates disease. These advances highlight opportunities for novel therapeutic strategies that aim to re-establish tolerance in patients with chronic allergic diseases by promoting Treg cell stability and function. PMID:27596705

  7. Lung disease - resources

    MedlinePlus

    Resources - lung disease ... The following organizations are good resources for information on lung disease : American Lung Association -- www.lung.org National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov ...

  8. Climate change and allergic disease.

    PubMed

    Bielory, Leonard; Lyons, Kevin; Goldberg, Robert

    2012-12-01

    Allergies are prevalent throughout the United States and impose a substantial quality of life and economic burden. The potential effect of climate change has an impact on allergic disorders through variability of aeroallergens, food allergens and insect-based allergic venoms. Data suggest allergies (ocular and nasal allergies, allergic asthma and sinusitis) have increased in the United States and that there are changes in allergies to stinging insect populations (vespids, apids and fire ants). The cause of this upward trend is unknown, but any climate change may induce augmentation of this trend; the subspecialty of allergy and immunology needs to be keenly aware of potential issues that are projected for the near and not so distant future.

  9. The inflammatory nature of allergic disease.

    PubMed

    Durham, S R

    1998-12-01

    The allergic inflammatory response in allergic rhinitis has been studied extensively owing to the high frequency of the condition, the significant morbidity it causes and the accessibility of the nasal tissue. The allergic inflammatory response is characterized by IgE synthesis, IgE-dependent mast cell activation and infiltration of the nasal mucosa by T lymphocytes and eosinophils. The immediate-phase response is mediated by a range of inflammatory mediators (such as histamine, leukotrienes and prostaglandins), resulting in vasodilatation, oedema, mucus secretion, itching and sneezing. Individuals who experience a late-phase response have further nasal symptoms 4-24 h after the initial challenge with allergen. Results of nasal biopsy studies indicate that the late-phase allergic response involves T-lymphocyte activation, production of TH2-type cytokines and tissue eosinophilia. Corticosteroids potently inhibit T-lymphocyte responses, and clinical studies in subjects with allergic rhinitis have demonstrated that they are extremely effective in blocking both early- and late-phase allergic reactions. Topical aqueous triamcinolone acetonide nasal spray represents a novel formulation of a topical corticosteroid for the treatment of allergic rhinitis. Data from controlled clinical studies indicate that it is effective in treating seasonal and perennial disease, is well tolerated, does not suppress adrenocortical function, is odourless, and can be administered as a once-daily dose. PMID:9988430

  10. Allergic Disease and Autoimmune Effectors Pathways

    PubMed Central

    Rottem, Menachem; Gershwin, M. Eric; Shoenfeld, Yehuda

    2002-01-01

    Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions. PMID:12885156

  11. Epigenetic regulation of asthma and allergic disease

    PubMed Central

    2014-01-01

    Epigenetics of asthma and allergic disease is a field that has expanded greatly in the last decade. Previously thought only in terms of cell differentiation, it is now evident the epigenetics regulate many processes. With T cell activation, commitment toward an allergic phenotype is tightly regulated by DNA methylation and histone modifications at the Th2 locus control region. When normal epigenetic control is disturbed, either experimentally or by environmental exposures, Th1/Th2 balance can be affected. Epigenetic marks are not only transferred to daughter cells with cell replication but they can also be inherited through generations. In animal models, with constant environmental pressure, epigenetically determined phenotypes are amplified through generations and can last up to 2 generations after the environment is back to normal. In this review on the epigenetic regulation of asthma and allergic diseases we review basic epigenetic mechanisms and discuss the epigenetic control of Th2 cells. We then cover the transgenerational inheritance model of epigenetic traits and discuss how this could relate the amplification of asthma and allergic disease prevalence and severity through the last decades. Finally, we discuss recent epigenetic association studies for allergic phenotypes and related environmental risk factors as well as potential underlying mechanisms for these associations. PMID:24932182

  12. Ambient air pollution and allergic diseases in children.

    PubMed

    Kim, Byoung-Ju; Hong, Soo-Jong

    2012-06-01

    The prevalence of allergic diseases has increased worldwide, a phenomenon that can be largely attributed to environmental effects. Among environmental factors, air pollution due to traffic is thought to be a major threat to childhood health. Residing near busy roadways is associated with increased asthma hospitalization, decreased lung function, and increased prevalence and severity of wheezing and allergic rhinitis. Recently, prospective cohort studies using more accurate measurements of individual exposure to air pollution have been conducted and have provided definitive evidence of the impact of air pollution on allergic diseases. Particulate matter and ground-level ozone are the most frequent air pollutants that cause harmful effects, and the mechanisms underlying these effects may be related to oxidative stress. The reactive oxidative species produced in response to air pollutants can overwhelm the redox system and damage the cell wall, lipids, proteins, and DNA, leading to airway inflammation and hyper-reactivity. Pollutants may also cause harmful effects via epigenetic mechanisms, which control the expression of genes without changing the DNA sequence itself. These mechanisms are likely to be a target for the prevention of allergies. Further studies are necessary to identify children at risk and understand how these mechanisms regulate gene-environment interactions. This review provides an update of the current understanding on the impact of air pollution on allergic diseases in children and facilitates the integration of issues regarding air pollution and allergies into pediatric practices, with the goal of improving pediatric health.

  13. Outdoor air pollution in urban areas and allergic respiratory diseases.

    PubMed

    D'Amato, G

    1999-12-01

    Respiratory allergic diseases (rhinitis, rhinosinusitis, bronchial asthma and its equivalents) appear to be increasing in most countries, and subjects living in urban and industrialized areas are more likely to experience respiratory allergic symptoms than those living in rural areas. This increase has been linked, among various factors, to air pollution, which is now an important public health hazard. Laboratory studies confirm the epidemiological evidence that inhalation of some pollutants, either individually or in combination, adversely affect lung function in asthmatics. The most abundant air pollutants in urban areas with high levels of vehicle traffic are respirable particulate matter, nitrogen dioxide and ozone. While nitrogen dioxide does not exert consistent effects on lung function, ozone, respirable particulate matter and allergens impair lung function and lead to increased airway responsiveness and bronchial obstruction in predisposed subjects. However, besides acting as irritants, airborne pollutants can modulate the allergenicity of antigens carried by airborne particles. By attaching to the surface of pollen grains and of plant-derived paucimicronic particles, pollutants can modify the morphology of these antigen-carrying agents and after their allergenic potential. In addition, by inducing airway inflammation, which increases airway epithelial permeability, pollutants overcome the mucosal barrier and so facilitate the allergen-induced inflammatory responses. Moreover, air pollutants such as diesel exhaust emissions are thought to modulate the immune response by increasing immunoglobulin E synthesis, thus facilitating allergic sensitization in atopic subjects and the subsequent development of clinical respiratory symptoms. PMID:10695313

  14. Rheumatoid lung disease

    MedlinePlus

    Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Elsevier Saunders; 2016:chap 65. Lake F, Proudman S. Rheumatoid arthritis and lung disease: from mechanisms to a practical approach. Semin Respir ...

  15. Interstitial Lung Diseases

    MedlinePlus

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to ... air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...

  16. Allergic rhinoconjunctivitis: burden of disease.

    PubMed

    Blaiss, Michael S

    2007-01-01

    Even though there is no mortality associated with allergic rhinoconjunctivitis (AR), there is significant morbidity in sufferers of this condition. The exact number of patients with AR is difficult to ascertain, with studies showing ranges from 9 to 42% of the population. Recently, the Allergies in America survey found that 14.2% of the adult U.S. population has been diagnosed with AR. It is well established that AR has a profound influence on the patient's quality of life. Not only do people with AR complain of rhinorrhea, nasal congestion, sneezing, itching, and associated eye problems disturbing, but they also have impaired emotional wellbeing and social functioning. Costs are a major burden in AR studies showing at least $6 billion/year. Although most attention related to costs in AR have been evaluating direct costs due to physician consultation and medical treatment, it is now clear that indirect costs are a major aspect of total costs in AR, especially for American businesses. Indirect costs include absenteeism from work or school because of illness and decreased productivity when at work or presenteeism. AR should be treated seriously by the medical community. Proper treatment of AR patients should not only greatly improve their quality of life, but also bring down health care costs, especially indirect ones, associated with this condition. PMID:17883905

  17. Interstitial lung disease

    MedlinePlus

    Diffuse parenchymal lung disease; Alveolitis; Idiopathic pulmonary pneumonitis (IPP) ... The lungs contain tiny air sacs (alveoli), which is where oxygen is absorbed. These air sacs expand with each ...

  18. Preventing atopy and allergic disease.

    PubMed

    Heine, Ralf G

    2014-01-01

    Due to the recent exponential increase in food allergies and atopic disorders, effective allergy prevention has become a public health priority in many developed regions. Important preventive strategies include the promotion of breastfeeding and vaginal deliveries, judicious use of perinatal antibiotics, as well as the avoidance of maternal tobacco smoking. Breastfeeding for at least 6 months and introduction of complementary solids from 4-6 months are generally recommended. Complex oligosaccharides in breast milk support the establishment of bifidobacteria in the neonatal gut which stimulate regulatory T lymphocyte responses and enhance tolerance development. Maternal elimination diets during pregnancy or lactation are not effective in preventing allergies. If exclusive breastfeeding is not possible, (supplemental) feeding with a partially hydrolyzed whey-based formula or extensively hydrolyzed casein-based formula may reduce the risk of cow's milk allergy and atopic dermatitis in infants with a family history of atopy. By contrast, asthma and allergic rhinitis at 4-6 years of age are not prevented by this approach. Soy formula and amino acid-based formula have no proven role in allergy prevention. Perinatal supplementation with probiotics and/or prebiotics may reduce the risk of atopic dermatitis, but no reliable effect on the prevention of food allergy or respiratory allergies has so far been found. A randomized trial on maternal fish oil supplementation during pregnancy found that atopic dermatitis and egg sensitization in the first year of life were significantly reduced, but no preventive effect for food allergies was demonstrated. The role of vitamin D deficiency or excess as a risk factor for food allergy and atopic disorders requires further study.

  19. Preventing atopy and allergic disease.

    PubMed

    Heine, Ralf G

    2014-01-01

    Due to the recent exponential increase in food allergies and atopic disorders, effective allergy prevention has become a public health priority in many developed regions. Important preventive strategies include the promotion of breastfeeding and vaginal deliveries, judicious use of perinatal antibiotics, as well as the avoidance of maternal tobacco smoking. Breastfeeding for at least 6 months and introduction of complementary solids from 4-6 months are generally recommended. Complex oligosaccharides in breast milk support the establishment of bifidobacteria in the neonatal gut which stimulate regulatory T lymphocyte responses and enhance tolerance development. Maternal elimination diets during pregnancy or lactation are not effective in preventing allergies. If exclusive breastfeeding is not possible, (supplemental) feeding with a partially hydrolyzed whey-based formula or extensively hydrolyzed casein-based formula may reduce the risk of cow's milk allergy and atopic dermatitis in infants with a family history of atopy. By contrast, asthma and allergic rhinitis at 4-6 years of age are not prevented by this approach. Soy formula and amino acid-based formula have no proven role in allergy prevention. Perinatal supplementation with probiotics and/or prebiotics may reduce the risk of atopic dermatitis, but no reliable effect on the prevention of food allergy or respiratory allergies has so far been found. A randomized trial on maternal fish oil supplementation during pregnancy found that atopic dermatitis and egg sensitization in the first year of life were significantly reduced, but no preventive effect for food allergies was demonstrated. The role of vitamin D deficiency or excess as a risk factor for food allergy and atopic disorders requires further study. PMID:24504215

  20. Occupational Exposure to Urban Air Pollution and Allergic Diseases

    PubMed Central

    Vimercati, Luigi; Gatti, Maria Franca; Baldassarre, Antonio; Nettis, Eustachio; Favia, Nicola; Palma, Marco; Martina, Gabriella Lucia Maria; Di Leo, Elisabetta; Musti, Marina

    2015-01-01

    Exposure to air pollution is associated with increased morbidity from cardiovascular diseases, lung cancer, respiratory and allergic diseases. The aim of this study was to investigate allergic diseases in 111 traffic wardens compared to a control group of 101 administrative employees. All participating subjects underwent a physical examination, in which a complete medical history was taken and a dedicated allergological questionnaire administered. Spirometry, Specific IgE dosage (RAST) and skin prick tests (SPT) were done. Diagnostic investigations such as the nasal cytology, a specific nasal provocation test and rhinomanometry were also performed. Statistical analyses were performed using STATA version 11. The percentage of subjects with a diagnosis of allergy was higher in the exposed workers than in the controls. As regards the clinical tests, the positivity was higher for the group of exposed subjects. Among the exposed workers, those who worked on foot or motorcycle had a higher positivity in clinical trials compared to the traffic wardens who used the car. Our study showed a higher percentage of allergic subjects in the group of workers exposed to outdoor pollutants than in the controls. These results suggest that allergological tests should be included in the health surveillance protocols for workers exposed to outdoor pollutants. PMID:26501303

  1. Mast Cells in Allergic Diseases and Mastocytosis

    PubMed Central

    Marquardt, Diana L.; Wasserman, Stephen I.

    1982-01-01

    Mast cells with their stores of vasoactive and chemotactic mediators are central to the pathogenesis of allergic diseases. The cross-linking of receptorbound IgE molecules on the surface of mast cells initiates a complex chain of events, including calcium ion influx, phospholipid methylation and turnover and cyclic nucleotide metabolism, ultimately resulting in the release of mediators of immediate hypersensitivity. These mast cell mediators are important in smooth muscle reactivity, in the recruitment of eosinophilic and neutrophilic leukocytes and in the generation of secondary chemical mediators. Histologic evidence of mast cell degranulation, biochemical evidence of mast cell mediators in blood and tissues and clinical evidence of signs and symptoms reproducible by these mediators have strongly supported the crucial role of mast cells in asthma, urticaria, anaphylaxis, rhinitis and mastocytosis. Because of their unique location at host environment interfaces, mast cells may both participate in allergic diseases and promote homeostasis. ImagesFigure 1.Figure 2.Figure 3. PMID:6293204

  2. [Probiotics in allergic diseases of childhood].

    PubMed

    Hauer, A

    2006-08-31

    The increase in allergic diseases in children in the industrialized countries is attributed, among things, to the "exaggerated hygiene" in early childhood typical of western lifestyle, since insufficient microbial exposure in this phase would appear to promote the development of allergies ("hygiene hypothesis"). Experimental data and initial results of clinical studies show that the immune system of infants can be stimulated by the endogenous intestinal flora. Probiotics, (apathogenic organisms present in human intestinal flora) have a very similar effect: Infants at risk of developing atopy, who, in the first 6 months of life received a special probiotic, contracted atopic dermatitis after two years only half as frequently as a control group of infants. Therapeutic effects were also observed in this clinical condition. For no other allergic manifestations have reports so far been published on the successful use of probiotics for prevention or treatment.

  3. Lung Diseases

    MedlinePlus

    ... on Carcinogens: Captafol A Human Health Perspective on Climate Change (Full Report) (4MB) Certain Glass Wool Fibers (Inhalable) ( ... Environmental Public Health (PEPH) (1MB) Programs and Initiatives: Climate Change and Human Health Respiratory Disease and the Environment ( ...

  4. Hyaluronan fragments as mediators of inflammation in allergic pulmonary disease

    PubMed Central

    Ghosh, Sumit; Hoselton, Scott A.; Dorsam, Glenn P.; Schuh, Jane M.

    2015-01-01

    Asthma is frequently caused and/or exacerbated by sensitization to allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen, leading to a disease course that is often very difficult to treat with standard asthma therapies. As a result of interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to allergens may experience a greater degree of tissue injury followed by airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. In addition, turnover of extracellular matrix (ECM) components is a hallmark of tissue injury and repair. This review focuses on the role of the glycosaminoglycan hyaluronan (HA), a component of the ECM, in pulmonary injury and repair with an emphasis on allergic asthma. Both the synthesis and degradation of the ECM are critical contributors to tissue repair and remodeling. Fragmented HA accumulates during tissue injury and functions in ways distinct from the larger native polymer. There is gathering evidence that HA degradation products are active participants in stimulating the expression of inflammatory genes in a variety of immune cells at the injury site. In this review, we will consider recent advances in the understanding of the mechanisms that are associated with HA accumulation and inflammatory cell recruitment in the asthmatic lung. PMID:25582403

  5. Oscar Wilde's skin disease: allergic contact dermatitis?

    PubMed

    Nater, J P

    1992-07-01

    During the last years of his life, Oscar Wilde (1856-1900) suffered from a suppurating otitis media as well as from an unidentified skin disease. The eruption was localized to his face, arms, chest and back and itched severely. A new theory is suggested, based on the fact that Wilde almost certainly used a dye to conceal his rapidly graying hair. He sensitized himself to p-phenylenediamine and developed a stubborn allergic contact dermatitis. Patch testing, the only proof of such a diagnosis, had not yet been devised.

  6. Lung Diseases and Conditions

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Lung Diseases and Conditions Breathing is a complex process. ... your bronchial tubes ( bronchitis ) or deep in your lungs ( pneumonia ). These infections cause a buildup of mucus ...

  7. Vitamin D and the development of allergic disease: how important is it?

    PubMed Central

    Mirzakhani, Hooman; Al-Garawi, Amal; Weiss, Scott T.; Litonjua, Augusto A.

    2015-01-01

    Summary Vitamin D has known effects on lung development and the immune system that may be important in the development, severity and course of allergic diseases (asthma, eczema and food allergy). Vitamin D deficiency is prevalent worldwide and may partly explain the increases in asthma and allergic diseases that have occurred over the last 50–60 years. In this review we explore past and current knowledge on the effect of vitamin D on lung development and immunomodulation and present the evidence of its role in allergic conditions. While there is growing observational and experimental evidence for the role of vitamin D, well-designed and well-powered clinical trials are needed to determine whether supplementation of vitamin D should be recommended in these disorders. PMID:25307157

  8. The impact of diet on asthma and allergic diseases.

    PubMed

    Julia, Valerie; Macia, Laurence; Dombrowicz, David

    2015-05-01

    The incidence of allergic diseases is increasing, both in developed and developing countries, concomitantly with the rise in living standards and the adoption of a 'western lifestyle'. For two decades, the hygiene hypothesis - which proposes that the lack of early childhood exposure to infectious agents increases susceptibility to allergic diseases in later life - provided the conceptual framework for unravelling the mechanisms that could account for the increased incidence of allergic diseases. In this Review, we discuss recent evidence that highlights the role of diet as a key factor influencing immune homeostasis and the development of allergic diseases through a complex interplay between nutrients, their metabolites and immune cell populations. Although further investigations are still required to understand these complex relationships, recent data have established a possible connection between metabolic homeostasis and allergic diseases.

  9. [Prevention of allergic diseases in childhood: from theory to reality].

    PubMed

    2016-06-01

    Allergic diseases have an increasing worldwide prevalence and a great impact on the health related costs. The research is focused on the study of etiological and risk factors of allergic diseases that can potentially be modified with primary, secondary and tertiary prevention strategies. Many of these measures do not have a definitively proven effect taking place in a controlled context different to what happens in real life. This paper aims to review the latest evidence on prevention of allergic diseases considering certainties and unresolved issues and focuses mainly on environmental, dietary, pharmacological and immunological preventive strategies for different levels of prevention. It is imperative to have a better understanding of genetic and environmental factors that cause allergic diseases to optimize preventive measures that are effective in reversing the increasing trend in the prevalence of allergic illnesses in childhood.

  10. Interstitial lung disease - adults - discharge

    MedlinePlus

    Diffuse parenchymal lung disease - discharge; Alveolitis - discharge; Idiopathic pulmonary pneumonitis - discharge; IPP - discharge; Chronic interstitial lung - discharge; Chronic respiratory interstitial lung - ...

  11. Respiratory effects of air pollution on allergic disease

    SciTech Connect

    Pierson, W.E.; Koenig, J.Q. )

    1992-10-01

    Allergic patients have an increased susceptibility to the adverse effects of both natural and man-made air pollutants. This goes for both indoor and outdoor air pollutants and manifests itself with biochemical, cellular, and pathophysiologic expressions of adverse health effects in allergic individuals. Also occupationally induced allergic diseases will remain very important. This area has been reviewed recently by Cullen et al. Since allergic patients comprise somewhere between 15% and 20% of the population, this increased susceptibility is of crucial importance not only for medical care and research but for legislative and regulatory consideration to protect these vulnerable individuals.108 references.

  12. Tropical parasitic lung diseases.

    PubMed

    Vijayan, V K

    2008-01-01

    Though parasitic lung diseases are frequently seen in tropical countries, these are being increasingly reported from many parts of the world due to globalisation and travel across the continents. In addition, the emergence of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS), the frequent use of immunosuppressive drugs in many diseases and the increasing numbers of organ transplantations have resulted in a renewed interest in many tropical parasitic lung diseases. This review outlines the recent developments in the pathogenesis, diagnosis and management of common and rare parasitic lung diseases.

  13. Lung disease in farmers.

    PubMed Central

    Warren, C. P.

    1977-01-01

    Lung diseases in farmers attributable to their occupation include (a) farmer's lung, caused by exposure to mouldy hay, (b) the asthma caused by exposure to grain dust and (c) silo-filler's disease. Their prevalence in Canada is unknown. Farmer's lung results from inhalation of mould spores in hay; the mechanism is immunologic. The exact cause and mechanism of grain dust asthma are unknown but may be immunologic. Silo-filler's disease is caused by the toxic effects of inhaled nitrogen dioxide. PMID:321110

  14. The relationship between autoimmunity and specific immunotherapy for allergic diseases

    PubMed Central

    Bozek, Andrzej; Kołodziejczyk, Krzysztof; Bednarski, Piotr

    2015-01-01

    The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1±12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this long-term observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term. PMID:26431066

  15. Gut Microbiota and Allergic Disease. New Insights.

    PubMed

    Lynch, Susan V

    2016-03-01

    The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy. PMID:27027953

  16. Novel delivery systems for anti-allergic agents: allergic disease and innovative treatments.

    PubMed

    Lopes, Carla M; Coelho, Pedro B; Oliveira, Rita

    2015-01-01

    Anti-allergic agents are used to treat a great variety of diseases which usually involve an inflammation reaction. These compounds act by inhibiting the release and the effects of inflammatory mediators (e.g. histamine) in the target tissue. The purpose of anti-allergy therapy is to deliver the drug to its local of action in a therapeutic concentration, minimizing the undesired side effects. In order to solve some of the anti-allergic agents' physicochemical drawbacks and the limitations associated to conventional pharmaceutical formulations (e.g. poor solubility and absorption, skin permeation, stability), novel drug delivery systems, such as cyclodextrins, liposomes, micelles, microemulsions, nano and microparticles, have been developed. Depending on the allergic condition, several administration routes are used to deliver anti-allergic agents, each with its own disadvantages to overcome. In the literature, there are a vast number of papers concerning novel delivery systems for anti-allergic agents, making it difficult to evaluate the information and the promising outcomes. The aim of the present review article is to compile the recent (i.e. in the new millennium) improvements of novel drug delivery technology focusing on the achievement of anti-allergic therapeutic delivery. The potential intrinsic benefits of these systems will reflect an increased therapeutic adherence and better patients' life quality. A critical prospect of future clinical trial directions will also be discussed. PMID:25895551

  17. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  18. Reflux and Lung Disease

    MedlinePlus

    ... Reflux and Lung Disease Proper Hydration Sodium Dangers Plant-Based Diets Why Breakfast Matters Patients & Visitors Giving For Professionals About Us Treatment & Programs Health Insights Doctors & Departments Research & Science Education & Training Make an Appointment Make a Donation ...

  19. Responses of Six-Weeks Aquatic Exercise on the Autonomic Nervous System, Peak Nasal Inspiratory Flow and Lung Functions in Young Adults with Allergic Rhinitis.

    PubMed

    Janyacharoen, Taweesak; Kunbootsri, Narupon; Arayawichanon, Preeda; Chainansamit, Seksun; Sawanyawisuth, Kittisak

    2015-06-01

    Allergic rhinitis is a chronic respiratory disease. Sympathetic hypofunction is identified in all of the allergic rhinitis patients. Moreover, allergic rhinitis is associated with decreased peak nasal inspiratory flow (PNIF) and impaired lung functions. The aim of this study was to investigate effects of six-week of aquatic exercise on the autonomic nervous system function, PNIF and lung functions in allergic rhinitis patients. Twenty-six allergic rhinitis patients, 12 males and 14 females were recruited in this study. Subjects were diagnosed by a physician based on history, physical examination, and positive reaction to a skin prick test. Subjects were randomly assigned to two groups. The control allergic rhinitis group received education and maintained normal life. The aquatic group performed aquatic exercise for 30 minutes a day, three days a week for six weeks. Heart rate variability, PNIF and lung functions were measured at the beginning, after three weeks and six weeks. There were statistically significant increased low frequency normal units (LF n.u.), PNIF and showed decreased high frequency normal units (HF n.u.) at six weeks after aquatic exercise compared with the control group. Six weeks of aquatic exercise could increase sympathetic activity and PNIF in allergic rhinitis patients.

  20. Indium Lung Disease

    PubMed Central

    Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen

    2012-01-01

    Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies. PMID:22207675

  1. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2015-12-07

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk.

  2. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2016-02-01

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. PMID:26644379

  3. Immunoregulatory Role of HLA-G in Allergic Diseases

    PubMed Central

    Contini, Paola; Negrini, Simone; Ciprandi, Giorgio; Puppo, Francesco

    2016-01-01

    Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. PMID:27413762

  4. Immunoregulatory Role of HLA-G in Allergic Diseases.

    PubMed

    Murdaca, Giuseppe; Contini, Paola; Negrini, Simone; Ciprandi, Giorgio; Puppo, Francesco

    2016-01-01

    Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation. PMID:27413762

  5. Alveolar macrophages from allergic lungs are not committed to a pro-allergic response and can reduce airway hyperresponsiveness following ex vivo culture

    PubMed Central

    Pouliot, P.; Spahr, A.; Careau, É.; Turmel, V.; Bissonnette, E. Y.

    2016-01-01

    Summary Background We already demonstrated that adoptive transfer of alveolar macrophages (AMs) from non-allergic rats into AM-depleted allergic rats prevents airway hyperresponsiveness (AHR). We also showed that AMs from non-sensitized, but not from sensitized, allergy-prone rats can prevent AHR following allergen challenge in sensitized allergic animals, establishing the importance of rat immunological status on the modulation of AM functions and suggesting that an allergic lung environment alters AM functions. Objective We investigated how the activation of allergic AMs can be modulated to reinstitute them with their capacity to reduce AHR. Methods AMs from sensitized Brown Norway rats were cultured ex vivo for up to 18 h in culture media to deprogram them from the influence of the allergic lung before being reintroduced into the lung of AM-depleted sensitized recipient. AHR and cytokines in bronchoalveolar lavage (BAL) were measured following allergen challenge. AMs stimulated ex vivo with Bacillus Calmette-Guerin(BCG) were used as positive controls as BCG induces a T-helper type 1 activation in AMs. Results AMs ex vivo cultured for 4–18 h reduced AHR to normal level. Interestingly, pro-allergic functions of AMs were dampened by 18 h culture and they reduced AHR even after spending 48 h in an allergic lung microenvironment. Furthermore, transfer of cultured AMs caused an increase in the levels of IFN-γ and IL-12 in BAL when compared with their ovalbumin control. After 18 h of ex vivo culture, AMs expressed reduced levels of TNF, IL-1α, IL-6, and Arginase-2 mRNAs compared with freshly isolated AMs, suggesting that ex vivo culture exempted AMs from lung stimuli that affected their functions. Conclusions There is a significant crosstalk between lung microenvironment and AMs, affecting their functions. It is also the first report showing that sensitized AMs can be modulated ex vivo to reduce lung pro-allergic environment, opening the way to therapies targetting

  6. Mitochondria in Lung Diseases

    PubMed Central

    Aravamudan, Bharathi; Thompson, Michael A.; Pabelick, Christina M.; Prakash, Y. S.

    2014-01-01

    Summary Mitochondria are autonomous cellular organelles that oversee a variety of functions such as metabolism, energy production, calcium buffering, and cell fate determination. Regulation of their morphology and diverse activities beyond energy production are being recognized as playing major roles in cellular health and dysfunction. This review is aimed at summarizing what is known regarding mitochondrial contributions to pathogenesis of lung diseases. Emphasis is given to understanding the importance of structural and functional aspects of mitochondria in both normal cellular function (based on knowledge from other cell types) and in development and modulation of lung diseases such as asthma, COPD, cystic fibrosis and cancer. Emerging techniques that allow examination of mitochondria, and potential strategies to target mitochondria in the treatment of lung diseases are also discussed. PMID:23978003

  7. Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice.

    PubMed

    de Boer, Johannes D; Berkhout, Lea C; de Stoppelaar, Sacha F; Yang, Jack; Ottenhoff, Roelof; Meijers, Joost C M; Roelofs, Joris J T H; van't Veer, Cornelis; van der Poll, Tom

    2015-10-15

    Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology (P < 0.05) and decreased IL-4 levels (P < 0.01), without influencing other HDM-induced responses. Considering the limited effects of dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.

  8. [Interstitial lung diseases].

    PubMed

    Mazzoccoli, Gianluigi; Carughi, Stefano; De Cata, Angelo; Giuliani, Antonio; Masciale, Nunzia; La Viola, Marco; Puzzolante, Felice; Balzanelli, Mario

    2003-05-01

    Interstitial lung diseases (ILD) are an heterogeneous group of inflammatory diseases characterized by an anatomical distortion of peripheral airways and interstitium, determined by a first stage of alveolitis and a following stage of fibrosis. Natural history of several ILD is characterized by slow and progressive destruction of alveolar-capillary functional units, often with respiratory failure and death. For their smoldering evolution and not specificity of symptoms (exertional dyspnea and cough) ILD may remain not diagnosed and not treated for a long time.

  9. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and

  10. Weighted Road Density and Allergic Disease in Children at High Risk of Developing Asthma

    PubMed Central

    Hansell, Anna L.; Rose, Nectarios; Cowie, Christine T.; Belousova, Elena G.; Bakolis, Ioannis; Ng, Kitty; Toelle, Brett G.; Marks, Guy B.; Almqvist, plus Catarina; Ampon, Rosario D; Ayer, Julian; Bird, Tessa; Brew, Bronwyn K; Britton, Warwick J; Celermajer, David; Cowell, Christopher T; Crisafulli, Daniele; Criss, Sally; Davis, Stella; Nabil Ezz, Wafaa; Forbes, Samantha; Garden, Frances L; Kemp, Andrew S; Knezevic, Natalia; Krause, William; Leeder, Stephen R; Mellis, Craig M; Mihrshahi, Seema; Neumann, Mark; Peat, Jennifer K; Quinones-Lucio, Andres; Skilton, Michael; Tattam, Anne; Tovey, Euan R; Vanlaar, Carl H.; Vukasin, Nicola; Wainwright, Craig; Webb, Karen L; Weber-Chrysochoou, Christina; Woolcock, Ann J; Zhou, Jie

    2014-01-01

    Background Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma. Methods We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis. Results Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06–1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01–1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03–1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children. Conclusion Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma. PMID:24949625

  11. Subclinical Interstitial Lung Disease

    PubMed Central

    Doyle, Tracy J.; Hunninghake, Gary M.

    2012-01-01

    The widespread use of high-resolution computed tomography in clinical and research settings has increased the detection of interstitial lung abnormalities (ILA) in asymptomatic and undiagnosed individuals. We reported that in smokers, ILA were present in about 1 of every 12 high-resolution computed tomographic scans; however, the long-term significance of these subclinical changes remains unclear. Studies in families affected with pulmonary fibrosis, smokers with chronic obstructive pulmonary disease, and patients with inflammatory lung disease have shown that asymptomatic and undiagnosed individuals with ILA have reductions in lung volume, functional limitations, increased pulmonary symptoms, histopathologic changes, and molecular profiles similar to those observed in patients with clinically significant interstitial lung disease (ILD). These findings suggest that, in select at-risk populations, ILA may represent early stages of pulmonary fibrosis or subclinical ILD. The growing interest surrounding this topic is motivated by our poor understanding of the inciting events and natural history of ILD, coupled with a lack of effective therapies. In this perspective, we outline past and current research focused on validating radiologic, physiological, and molecular methods to detect subclinical ILD. We discuss the limitations of the available cross-sectional studies and the need for future longitudinal studies to determine the prognostic and therapeutic implications of subclinical ILD in populations at risk of developing clinically significant ILD. PMID:22366047

  12. Allergic diseases: the price of civilisational progress

    PubMed Central

    Sowa, Paweł; Rutkowska-Talipska, Joanna; Sulkowski, Stanisław; Rutkowski, Ryszard

    2014-01-01

    Atopic disorders are a major global health problem. The prevalence of asthma, allergic rhinitis and atopic dermatitis has been increasing over the last four decades, both in the industrialized and developing countries. It seems to be related to changes in the social structure, increasing industrialization, pollution and dietary changes. Many hypotheses link the allergy epidemic to stringent hygiene, dominance of a westernized lifestyle and an accelerated pace of life. Dietary antioxidants, lipids, sodium, vitamin D seem also to be implicated. We endeavour to review the most relevant theories with a special emphasis on the hygiene, antioxidative, lipid and air pollution hypotheses. It is however important to note that none of them explains all the aspects of unprecedented rise in the prevalence of allergic disorders. A complex interplay between host's immune response, invading pathogens, diversity of environmental factors and genetic background seems to be of a particular importance. Current allergy epidemic is multifactorial and basic and epidemiologic studies are warranted to further our understanding of this phenomenon. PMID:25097472

  13. [Indium lung disease].

    PubMed

    Nakano, Makiko; Omae, Kazuyuki

    2014-02-01

    "Indium lung" is a new occupational lung disease. The global demand for indium, the major material used in manufacturing flat-screen display panels, has skyrocketed since the 1990s (Japan comprises 85% of the worldwide demand). The first case was reported in Japan in 2003, followed by seven cases (interstitial pneumonia and emphysema) in Japan. Two pulmonary alveolar proteinosis (PAP) cases in the USA followed in 2011. Indium lung has been described as interstitial pneumonia, pneumothorax, emphysema, and PAP. In 2013, The Japan Ministry of Health, Labor and Welfare issued an "Ordinance on the Prevention of Hazards Due to Specified Chemical Substances" requiring employers to provide regular health checks for employees and measurements of work environment concentrations of respirable indium dust.

  14. Prevention of House Dust Mite Induced Allergic Airways Disease in Mice through Immune Tolerance

    PubMed Central

    Agua-Doce, Ana; Graca, Luis

    2011-01-01

    Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens. PMID:21818308

  15. Epidemiology and current status of allergic rhinitis, asthma, and associated allergic diseases in Korea: ARIA Asia-Pacific workshop report.

    PubMed

    Park, Hae Sim; Choi, Gil Soon; Cho, Joong Sang; Kim, You-Young

    2009-01-01

    The prevalence of allergic rhinitis and asthma has recently increased in Korea, and both conditions are recognized as major chronic respiratory diseases requiring active intervention. The prevalence of rhinitis among asthmatic patients is high, ranging from 60 to 80%, and could seriously affect asthma severity and outcome. We suggest that allergic rhinitis should be properly evaluated in asthmatic patients to achieve better asthma control.

  16. Allergic diseases among children: nutritional prevention and intervention.

    PubMed

    Hendaus, Mohamed A; Jomha, Fatima A; Ehlayel, Mohammad

    2016-01-01

    Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for

  17. Allergic diseases among children: nutritional prevention and intervention

    PubMed Central

    Hendaus, Mohamed A; Jomha, Fatima A; Ehlayel, Mohammad

    2016-01-01

    Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for

  18. Allergic diseases among children: nutritional prevention and intervention.

    PubMed

    Hendaus, Mohamed A; Jomha, Fatima A; Ehlayel, Mohammad

    2016-01-01

    Allergic diseases comprise a genetically heterogeneous group of chronic, immunomediated diseases. It has been clearly reported that the prevalence of these diseases has been on the rise for the last few decades, but at different rates, in various areas of the world. This paper discusses the epidemiology of allergic diseases among children and their negative impact on affected patients, their families, and societies. These effects include the adverse effects on quality of life and economic costs. Medical interest has shifted from tertiary or secondary prevention to primary prevention of these chronic diseases among high-risk infants in early life. Being simple, practical, and cost-effective are mandatory features for any candidate methods delivering these strategies. Dietary therapy fits this model well, as it is simple, practical, and cost-effective, and involves diverse methods. The highest priority strategy is feeding these infants breast milk. For those who are not breast-fed, there should be a strategy to maintain beneficial gut flora that positively influences intestinal immunity. We review the current use of probiotics, prebiotics, and synbiotics, and safety and adverse effects. Other dietary modalities of possible potential in achieving this primary prevention, such as a Mediterranean diet, use of milk formula with modified (hydrolyzed) proteins, and the role of micronutrients, are also explored. Breast-feeding is effective in reducing the risk of asthma, allergic rhinitis, and atopic eczema among children. In addition, breast milk constitutes a major source of support for gut microbe colonization, due to its bifidobacteria and galactooligosaccharide content. The literature lacks consensus in recommending the addition of probiotics to foods for prevention and treatment of allergic diseases, while prebiotics may prove to be effective in reducing atopy in healthy children. There is insufficient evidence to support soy formulas or amino acid formulas for

  19. [Preliminary results of prophylactic program of allergic diseases in children in Lodz district].

    PubMed

    Stelmach, Włodzimierz; Korzeniewska, Aleksandra; Piechota, Mariusz; Podsiadłowicz-Borzecka, Małgorzata; Majak, Paweł; Stelmach, Iwona

    2002-01-01

    Allergic diseases are one of the most important problems in medicine. As a consequence of increased frequency of allergic diseases, negative health, economical and social problems appear. To eliminate these consequences prophylactic programmes are created. In this paper preliminary results of Prophylactic Program of Allergic Diseases in Children in Łodz district in 2000-2001 years is presented. PMID:12884565

  20. The ocular surface: from physiology to the ocular allergic diseases.

    PubMed

    Galicia-Carreón, Jorge; Santacruz, Concepción; Hong, Enrique; Jiménez-Martínez, María C

    2013-01-01

    Allergic conjunctivitis (AC) is an inflammation of the conjunctiva secondary to an immune response to exogenous antigens, usually called allergens. In fact, AC is a syndrome that involves the entire ocular surface, including conjunctiva, lids, cornea, and tear film. The signs and symptoms of AC have a meaningful effect on comfort and patient health, and could be influenced by environment, genetics and immune regulation mechanisms, all of which work together in a complex immunological homeostasis. Dysregulation in such immune responses could turn into a variety of ocular allergic diseases (OAD). This review describes some of the current understanding of cellular and molecular pathways involved in different OAD.

  1. Role of sensitization to mammalian serum albumin in allergic disease.

    PubMed

    Liccardi, Gennaro; Asero, Riccardo; D'Amato, Maria; D'Amato, Gennaro

    2011-10-01

    Serum albumin (SA) constitutes an intriguing puzzle that is involved in allergic sensitizations from different sources and induces different clinical manifestations. In this article, we describe the role of sensitization to SAs in inducing allergic diseases and the complex interactions and cross-reactivity between SA resulting from its presence in various mammalian tissues and fluids. SAs alone are an uncommon cause of allergic sensitization in airways, but these allergenic proteins likely play a significant role as cross-reacting allergens in individuals sensitized to several types of animal dander. SAs are a minor allergen in milk but a major allergen in meats. Recently, bovine SA has been added to the culture medium of spermatozoids used for artificial insemination. As a consequence, some case reports have shown that bovine SA may be a causative agent in severe anaphylaxis after standard intrauterine insemination or in vitro fertilization. PMID:21809117

  2. Role of sensitization to mammalian serum albumin in allergic disease.

    PubMed

    Liccardi, Gennaro; Asero, Riccardo; D'Amato, Maria; D'Amato, Gennaro

    2011-10-01

    Serum albumin (SA) constitutes an intriguing puzzle that is involved in allergic sensitizations from different sources and induces different clinical manifestations. In this article, we describe the role of sensitization to SAs in inducing allergic diseases and the complex interactions and cross-reactivity between SA resulting from its presence in various mammalian tissues and fluids. SAs alone are an uncommon cause of allergic sensitization in airways, but these allergenic proteins likely play a significant role as cross-reacting allergens in individuals sensitized to several types of animal dander. SAs are a minor allergen in milk but a major allergen in meats. Recently, bovine SA has been added to the culture medium of spermatozoids used for artificial insemination. As a consequence, some case reports have shown that bovine SA may be a causative agent in severe anaphylaxis after standard intrauterine insemination or in vitro fertilization.

  3. Therapeutic targets in allergic eye disease.

    PubMed

    Bielory, L

    2001-01-01

    The objective of this article is to provide an overview of the present state of treatment of ocular allergy. Immuno-ophthalmology arose in the portion of this past century when investigators uncovered the uniqueness of the lens proteins and that it could induce an immunological response otherwise know as phacoanaphylaxis. Further studies have shown many similarities between the eye and other organ systems, but one of the most profound problems was the spring "catarrh" that involved the eyes and nose, i.e., rhinoconjunctivitis. Treatment over the past 10 years has expanded with the better understanding of the allergic response at the conjunctival surface. Allergen immunotherapy remains a cornerstone of treatment. In fact, the very first report of the use of immunotherapy in 1911 "measured the patient's resistance during experiments ... of pollen extracts to excite a conjunctival reaction" (Noon L, and Cantar BO, Lancet 1572-1573, 1911).

  4. The evaluation of allergens and allergic diseases in children.

    PubMed

    Lee, C S; Tang, R B; Chung, R L

    2000-12-01

    Knowing the incidence of allergic diseases and their relationship with allergens is a crucial requirement for therapeutic judgment. We present our experience on the incidence, clinical features and allergens of the allergic diseases detected by multiple allergosorbent chemiluminescent assay (MAST-CLA) in children from 1997 to 1999 at the Taipei Veterans General Hospital. The incidence of bronchial asthma, allergic rhinitis and atopic dermatitis are significantly different when stratified by age groups. Among the enrolled 2008 patients, 980 (48.8%) patients have positive MAST-CLA results. Of these, 562 (57.3%) are male and 418 (42.7%) are female. A significant increase among patients with positive allergens is also found when stratified by age group. Inhalant allergen is the major allergen detected in our patients. House dust mites Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), cockroaches, feathers, and dog dander show the highest incidence in the 7- to 12-year-old group. In the fungal group, Aspergillus and Penicillium also show a significant difference in the incidence among different age groups. Pollen allergens, on a whole, show significant difference in incidence among different age groups. The food allergen group shows variable significant difference in incidence. Crab, milk, and egg white show the highest significant incidence in the 2- to 6-year-old group. These results suggest that the incidence of allergens detected in allergic diseases varies among different age groups. PMID:11269366

  5. Gender Associated High Body Mass Index in Allergic Diseases

    PubMed Central

    Lokaj-Berisha, Violeta; Gacaferri-Lumezi, Besa; Minci–Bejtullahu, Ganimete; Latifi-Pupovci, Hatixhe; Karahoda–Gjurgjeala, Natyra; Berisha, Naser; Morina, Teuta

    2014-01-01

    BACKGROUND: The increasing prevalence of allergic diseases and atopy is affected by sex, age and lifestyle factors. Obesity and excess weight are reported to be potential risk factors for atopy and specifically for asthma symptoms in children and adults. OBJECTIVE: To assess the relation between body mass index (BMI) and allergic diseases in patients of both genders, as well as association of BMI with atopy in healthy subjects. METHODS: BMI (kg/m2), skin-prick test and total serum immunoglobulin E levels were assessed in 139 subjects: 109 were patients with allergic diseases (M to F ratio was 51:58) and 30 were healthy controls (M to F ratio was 6:24). RESULTS: The study population was grouped into asthma, asthmarhinitis, rhinitis, Urticaria oreczema and controls by BMI and sex. Females with the highest BMI were in asthma and urticaria/eczema group. Males with the highest BMI were in asthmarhinitis and urticariaeczema group. High BMI was associated with atopy in both genders of healthy controls. High levels of total IgE were in male allergic patients. CONCLUSION: High BMI was associated with asthma in females, urticaria/eczema in both genders and atopy in both genders of healthy controls. Higher levels of total IgE were concluded in male patients. PMID:27275199

  6. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

  7. Characterization of inflammatory cell infiltration in feline allergic skin disease.

    PubMed

    Taglinger, K; Day, M J; Foster, A P

    2007-11-01

    Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.

  8. Asbestos-related lung disease

    SciTech Connect

    Westerfield, B.T. )

    1992-06-01

    Asbestos is a versatile fibrous mineral that can cause lung disease and death. Asbestosis, benign pleural disease, lung cancer, and mesothelioma can all result from inhaling asbestos. The history of disease and exposure risks are discussed. The difficult assessment of risk and the long latency period for development of disease demand evaluation and regular surveillance of asbestos-exposed workers.22 references.

  9. Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice.

    PubMed Central

    Gavett, Stephen H; Haykal-Coates, Najwa; Copeland, Lisa B; Heinrich, Joachim; Gilmour, M Ian

    2003-01-01

    Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 micro m aerodynamic diameter; PM(2.5)) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM(2.5) from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM(2.5) from Hettstedt, but not PM(2.5) from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Hettstedt PM(2.5) whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only in allergic mice exposed to Hettstedt PM(2.5) before challenge. Both Hettstedt and Zerbst PM(2.5) significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM(2.5) influences the severity of allergic respiratory disease. PMID:12948886

  10. The Effects of Maternal Exposure to Bisphenol A on Allergic Lung Inflammation into Adulthood

    PubMed Central

    Lawrence, B. Paige

    2012-01-01

    Bisphenol A (BPA) is a high–production volume chemical classified as an environmental estrogen and used primarily in the plastics industry. BPA’s increased usage correlates with rising BPA levels in people and a corresponding increase in the incidence of asthma. Due to limited studies, the contribution of maternal BPA exposure to allergic asthma pathogenesis is unclear. Using two established mouse models of allergic asthma, we examined whether developmental exposure to BPA alters hallmarks of allergic lung inflammation in adult offspring. Pregnant C57BL/6 dams were gavaged with 0, 0.5, 5, 50, or 500 μg BPA/kg/day from gestational day 6 until postnatal day 21. To induce allergic inflammation, adult offspring were mucosally sensitized with inhaled ovalbumin containing low-dose lipopolysaccharide or ip sensitized using ovalbumin with alum followed by ovalbumin aerosol challenge. In the mucosal sensitization model, female offspring that were maternally exposed to ≥ 50 μg BPA/kg/day displayed enhanced airway lymphocytic and lung inflammation, compared with offspring of control dams. Peritoneally sensitized, female offspring exposed to ≤ 50 μg BPA/kg/day presented dampened lung eosinophilia, compared with vehicle controls. Male offspring did not exhibit these differences in either sensitization model. Our data demonstrate that maternal exposure to BPA has subtle and qualitatively different effects on allergic inflammation, which are critically dependent upon route of allergen sensitization and sex. However, these subtle, yet persistent changes due to developmental exposure to BPA did not lead to significant differences in overall airway responsiveness, suggesting that early life exposure to BPA does not exacerbate allergic inflammation into adulthood. PMID:22821851

  11. Interstitial lung disease.

    PubMed

    Cottin, Vincent

    2013-03-01

    This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear.

  12. Non-pulmonary allergic diseases and inflammatory bowel disease: A qualitative review

    PubMed Central

    Kotlyar, David S; Shum, Mili; Hsieh, Jennifer; Blonski, Wojciech; Greenwald, David A

    2014-01-01

    While the etiological underpinnings of inflammatory bowel disease (IBD) are highly complex, it has been noted that both clinical and pathophysiological similarities exist between IBD and both asthma and non-pulmonary allergic phenomena. In this review, several key points on common biomarkers, pathophysiology, clinical manifestations and nutritional and probiotic interventions for both IBD and non-pulmonary allergic diseases are discussed. Histamine and mast cell activity show common behaviors in both IBD and in certain allergic disorders. IgE also represents a key immunoglobulin involved in both IBD and in certain allergic pathologies, though these links require further study. Probiotics remain a critically important intervention for both IBD subtypes as well as multiple allergic phenomena. Linked clinical phenomena, especially sinonasal disease and IBD, are discussed. In addition, nutritional interventions remain an underutilized and promising therapy for modification of both allergic disorders and IBD. Recommending new mothers breastfeed their infants, and increasing the duration of breastfeeding may also help prevent both IBD and allergic diseases, but requires more investigation. While much remains to be discovered, it is clear that non-pulmonary allergic phenomena are connected to IBD in a myriad number of ways and that the discovery of common immunological pathways may usher in an era of vastly improved treatments for patients. PMID:25170192

  13. Lung disease in rheumatoid arthritis.

    PubMed

    Yunt, Zulma X; Solomon, Joshua J

    2015-05-01

    Rheumatoid arthritis (RA) affects approximately 1% of the US population frequently has extra-articular manifestations. Most compartments of the lung are susceptible to disease. Interstitial lung disease (ILD) and airways disease are the most common forms of RA-related lung disease. RA-ILD carries the worst prognosis and most often manifests in a histologic pattern of usual interstitial pneumonia or nonspecific interstitial pneumonia. There have been no large, well-controlled prospective studies investigating therapies for RA-ILD. Treatment usually entails immunomodulatory agents. Further studies are needed to better understand pathogenic mechanisms of disease that lead to lung involvement in these patients.

  14. [The role of immunotherapy in the prevention of allergic diseases].

    PubMed

    Lugović-Mihić, Liborija; Duvancić, Tomislav

    2011-01-01

    Immunotherapy through repeated administration of allergens and augmentation of doses (hyposensibilization) with the purpose of decreasing the severity of type I allergic reactions or even its complete elimination is known already for a longer period of time. This type of therapy is especially beneficial in allergies to Hymenoptera venom, allergic rhinoconjunctivitis, allergic asthma and is implemented in patients with previously proven allergy to appropriate allergens (insects, pollen, house dust mite, pet dander and other). The most common form of therapy is subcutaneous immunotherapy which includes a series of injections containing specific allergens (allergy vaccines) with increasingly larger doses administered subcutaneously during a period of 3-5 years. There are also other forms of immunotherapy (for instance sublingual immunotherapy) although these are less effective. Repetition of the hyposensibilization procedure leads to further reduction in severity of allergy disease in the majority of patients. The efficacy of immunotherapy is also proven by a lower risk of allergic rhinitis patients developing asthma as well as by prevention of new sensibilizations.

  15. Mitochondria in lung disease.

    PubMed

    Cloonan, Suzanne M; Choi, Augustine M K

    2016-03-01

    Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell's most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets.

  16. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported.

  17. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. PMID:27090934

  18. Modulation of immune responses by immunotherapy in allergic diseases.

    PubMed

    Cavkaytar, Ozlem; Akdis, Cezmi A; Akdis, Mübeccel

    2014-08-01

    Allergen immunotherapy (AIT) has been used for 100 years and until now different immunoregulatory pathways have been shown to take place in its mechanisms of action. It is characterized by administration of the causative allergen and is shown to be clinically efficient even after discontinuation of therapy particularly in allergic respiratory diseases, bee venom allergy, and food allergy. Generation of antigen/allergen-specific peripheral tolerance is the key mechanism during immunotherapy. It is mediated by development of T and B regulatory cells, IgG4 isotype allergen-specific antibodies and the involvement of multiple suppressor factors, which lead to decreased tissue inflammation, early and late phase responses. Describing novel regulatory mechanisms in the process of immune tolerance induction will help to identify treatment modalities not only for allergic disorders, but also for autoimmune diseases, organ transplantation, chronic infections, and cancer.

  19. What Are Asbestos-Related Lung Diseases?

    MedlinePlus

    ... the NHLBI on Twitter. What Are Asbestos-Related Lung Diseases? Asbestos-related lung diseases are diseases caused ... peritoneum (PER-ih-to-NE-um). Asbestos-Related Lung Diseases Figure A shows the location of the ...

  20. How Is Childhood Interstitial Lung Disease Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Childhood Interstitial Lung Disease Treated? Childhood interstitial lung disease (chILD) is ... prevent acid reflux, which can lead to aspiration. Lung Transplant A lung transplant may be an option ...

  1. Types of Childhood Interstitial Lung Disease

    MedlinePlus

    ... the NHLBI on Twitter. Types of Childhood Interstitial Lung Disease The broad term "childhood interstitial lung disease" ( ... affect are shown in the illustration below. Normal Lungs and Lung Structures Figure A shows the location ...

  2. CT in the diagnosis of interstitial lung disease

    SciTech Connect

    Bergin, C.J.; Mueller, N.L.

    1985-09-01

    The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT change in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.

  3. Characterization of NLRP12 during the Development of Allergic Airway Disease in Mice

    PubMed Central

    Allen, Irving C.; Lich, John D.; Arthur, Janelle C.; Jania, Corey M.; Roberts, Reid A.; Callaway, Justin B.; Tilley, Stephen L.; Ting, Jenny P.-Y.

    2012-01-01

    Among the 22 members of the nucleotide binding-domain, leucine rich repeat-containing (NLR) family, less than half have been functionally characterized. Of those that have been well studied, most form caspase-1 activating inflammasomes. NLRP12 is a unique NLR that has been shown to attenuate inflammatory pathways in biochemical assays and mediate the lymph node homing of activated skin dendritic cells in contact hypersensitivity responses. Since the mechanism between these two important observations remains elusive, we further evaluated the contribution of NLRP12 to organ specific adaptive immune responses by focusing on the lung, which, like skin, is exposed to both exogenous and endogenous inflammatory agents. In models of allergic airway inflammation induced by either acute ovalbumin (OVA) exposure or chronic house dust mite (HDM) antigen exposure, Nlrp12−/− mice displayed subtle differences in eosinophil and monocyte infiltration into the airways. However, the overall development of allergic airway disease and airway function was not significantly altered by NLRP12 deficiency. Together, the combined data suggest that NLRP12 does not play a vital role in regulating Th2 driven airway inflammation using common model systems that are physiologically relevant to human disease. Thus, the allergic airway inflammation models described here should be appropriate for subsequent studies that seek to decipher the contribution of NLRP12 in mediating the host response to agents associated with asthma exacerbation. PMID:22291998

  4. [Histamine H₁ receptor gene as an allergic diseases-sensitive gene and its impact on therapeutics for allergic diseases].

    PubMed

    Mizuguchi, Hiroyuki; Kitamura, Yoshiaki; Kondo, Yuto; Kuroda, Wakana; Yoshida, Haruka; Miyamoto, Yuko; Hattori, Masashi; Takeda, Noriaki; Fukui, Hiroyuki

    2011-02-01

    Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H₁ receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene.

  5. SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES

    SciTech Connect

    Diaz-Sanchez, David

    2000-08-20

    Most studies of the health effects of diesel exhaust have focused on the controversial issue of its role in cancer. However, recently the role of combustion products such as diesel exhaust particles (DEP) in modulating the immune response has garnered much attention. In particular the effect of DEP on allergic and asthmatic diseases has been the focus of many studies. A link between industrialization and allergic disease has long been presumed. Indeed, only 50 years after the first recorded reported case of allergy in 1819, Charles Blackely wrote that the ''hay-fever epidemic'' was associated with the movement of people from the country into the cities. Ishizaki et al. (1987) found that people in Japan living on busy roads lined with cedar trees have more allergies to cedar than residents living on similar streets with much less traffic. Since that time other epidemiological studies have reported similar findings. Kramer, et al., showed that hay fever is greater in residential areas with heavy truck traffic, while Weiland, et al., reported that allergic symptoms correlate with the distance of residences to roads with heavy traffic.

  6. [The role of immunoglobulin preparations in treatment of allergic diseases].

    PubMed

    Boznański, Andrzej; Widerska, Alicja

    2002-01-01

    Intravenous immunoglobulin (IVIG) has been used for many years to treat patients with primary immunodeficiencies. More recently, IVIG has been shown to have antiinflammatory activity when used at substantially higher concentrations. A number of studies have examined the efficacy of IVIG in allergic diseases. For patients with severe refractory asthma, sinusitis, atopic dermatitis, and urticaria, IVIG offers an alternative therapy with relatively few side effects. Although the mechanism by which IVIG may attenuate the allergic response is still undetermined, clinical studies have shown that immunoglobulin therapy can decrease serum IgE levels and increase glucocorticoid binding affinity, while in vitro studies have shown that IVIG can decrease T-cell secretion of TH2 cytokines.

  7. Epidermal RAF prevents allergic skin disease

    PubMed Central

    Raguz, Josipa; Jeric, Ines; Niault, Theodora; Nowacka, Joanna Daniela; Kuzet, Sanya Eduarda; Rupp, Christian; Fischer, Irmgard; Biggi, Silvia; Borsello, Tiziana; Baccarini, Manuela

    2016-01-01

    The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis-restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation. Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling: BRAF promotes ERK activation, while RAF1 dims stress kinase activation. In vivo, JNK inhibition prevents disease onset, while MEK/ERK inhibition in mice lacking epidermal RAF1 phenocopies it. These results support a primary role of keratinocytes in the pathogenesis of atopic dermatitis, and the animals lacking BRAF and RAF1 in the epidermis represent a useful model for this disease. DOI: http://dx.doi.org/10.7554/eLife.14012.001 PMID:27431613

  8. Effects of MK-801 and amphetamine treatments on allergic lung inflammatory response in mice.

    PubMed

    Hamasato, Eduardo Kenji; Ligeiro de Oliveira, Ana Paula; Lino-dos-Santos-Franco, Adriana; Ribeiro, Alison; Ferraz de Paula, Viviane; Peron, Jean Pierre Schatzmann; Damazo, Amílcar Sabino; Tavares-de-Lima, Wothan; Palermo-Neto, João

    2013-08-01

    Glutamate acts as a neurotransmitter within the Central Nervous System (CNS) and modifies immune cell activity. In lymphocytes, NMDA glutamate receptors regulate intracellular calcium, the production of reactive oxygen species and cytokine synthesis. MK-801, a NMDA receptor open-channel blocker, inhibits calcium entry into mast cells, thereby preventing mast cell degranulation. Several lines of evidence have shown the involvement of NMDA glutamate receptors in amphetamine (AMPH)-induced effects. AMPH treatment has been reported to modify allergic lung inflammation. This study evaluated the effects of MK-801 (0.25mg/kg) and AMPH (2.0mg/kg), given alone or in combination, on allergic lung inflammation in mice and the possible involvement of NMDA receptors in this process. In OVA-sensitized and challenged mice, AMPH and MK-801 given alone decreased cellular migration into the lung, reduced IL-13 and IL10 levels in BAL supernatant, reduced ICAM-1 and L-selectin expression in granulocytes in the BAL and decreased mast cell degranulation. AMPH treatment also decreased IL-5 levels. When both drugs were administered, treatment with MK-801 reversed the decrease in the number of eosinophils and neutrophils induced by AMPH in the BAL of OVA-sensitized and challenged mice as well as the effects on the expression of L-selectin and ICAM-1 in granulocytes, the IL-10, IL-5 and IL-13 levels in BAL supernatants and increased mast cell degranulation. At the same time, treatment with MK-801, AMPH or with MK-801+AMPH increased corticosterone serum levels in allergic mice. These results are discussed in light of possible indirect effects of AMPH and MK-801 via endocrine outflow from the CNS (i.e., HPA-axis activity) to the periphery and/or as a consequence of the direct action of these drugs on immune cell activity, with emphasis given to mast cell participation in the allergic lung response of mice.

  9. Lung function and airway diseases.

    PubMed

    Weiss, Scott T

    2010-01-01

    Two studies report genome-wide association studies for lung function, using cross-sectional spirometric measurements in healthy individuals. They identify six genetic loci newly associated to natural variation in lung function, which may have implications for the related airway diseases of asthma and chronic obstructive pulmonary disease. PMID:20037613

  10. Does aluminum smelting cause lung disease

    SciTech Connect

    Abramson, M.J.; Wlodarczyk, J.H.; Saunders, N.A.; Hensley, M.J.

    1989-04-01

    The evidence concerning a relationship between work in the aluminum industry and lung disease has been reviewed using epidemiologic criteria. Adequate data on environmental exposure are rarely presented. Case series on aluminum potroom workers over the past 50 years have identified an asthmalike syndrome that appears to be due to an irritant rather than an allergic mechanism. These studies have been supported by evidence of within shift variability of measures of lung function. However, to date, there is inadequate evidence to resolve the question of whether potroom exposure initiates asthma or merely precipitates asthmalike symptoms in a predisposed individual. Cross-sectional studies have demonstrated evidence of reduced lung function, consistent with chronic airflow limitation. In exposed aluminum smelter workers compared to unexposed control subjects. Cigarette smoking, the major potential confounding variable, has been measured and accounted for in multivariate analyses. To date, evidence is lacking from longitudinal studies about the development of disabling chronic obstructive lung disease. Exposure to coal tar pitch volatiles in the production and consumption of anodes has biologic plausibility for an association of lung cancer with work in an aluminum smelter. Although retrospective mortality studies have failed to account for the probable high prevalence of smoking in blue collar workers, the relative risk of lung cancer is very low if present at all. Pulmonary fibrosis has not been shown to be a significant problem in aluminum smelter workers. Future research in the aluminum industry needs to concentrate on longitudinal studies, preferably with an inception cohort for the investigation of potroom asthma. 92 references.

  11. Alterations of the Lung Methylome in Allergic Airway Hyper-Responsiveness

    PubMed Central

    Cheng, Robert YS; Shang, Yan; Limjunyawong, Nathachit; Dao, Tyna; Das, Sandhya; Rabold, Richard; Sham, James SK; Mitzner, Wayne; Tang, Wan-Yee

    2014-01-01

    Asthma is a chronic airway disorder characterized by recurrent attacks of breathlessness and wheezing, affecting 300 million people around the world (available at: www.who.int). To date, genetic factors associated with asthma susceptibility have been unable to explain the full etiology of asthma. Recent studies have demonstrated that the epigenetic disruption of gene expression plays an equally important role in the development of asthma through interaction with our environment. We sensitized 6-week-old C57BL/6J mice with house-dust-mite (HDM) extracts intraperitoneally followed by 5 weeks of exposure to HDM challenges (three times a week) intratracheally. HDM-exposed mice showed an increase in airway hyper-responsiveness (AHR) and inflammation together with structural remodeling of the airways. We applied methylated DNA immunoprecipitation-next generation sequencing (MeDIP-seq) for profiling of DNA methylation changes in the lungs in response to HDM. We observed about 20 million reads by a single-run of massive parallel sequencing. We performed bioinformatics and pathway analysis on the raw sequencing data to identify differentially methylated candidate genes in HDM-exposed mice. Specifically, we have revealed that the transforming growth factor beta signaling pathway is epigenetically modulated by chronic exposure to HDM. Here, we demonstrated that a specific allergen may play a role in AHR through an epigenetic mechanism by disrupting the expression of genes in lungs that might be involved in airway inflammation and remodeling. Our findings provide new insights into the potential mechanisms by which environmental allergens induce allergic asthma and such insights may assist in the development of novel preventive and therapeutic options for this debilitative disease. PMID:24446183

  12. Tracking of Inhaled Near-Infrared Fluorescent Nanoparticles in Lungs of SKH-1 Mice with Allergic Airway Inflammation.

    PubMed

    Markus, M Andrea; Napp, Joanna; Behnke, Thomas; Mitkovski, Miso; Monecke, Sebastian; Dullin, Christian; Kilfeather, Stephen; Dressel, Ralf; Resch-Genger, Ute; Alves, Frauke

    2015-12-22

    Molecular imaging of inflammatory lung diseases, such as asthma, has been limited to date. The recruitment of innate immune cells to the airways is central to the inflammation process. This study exploits these cells for imaging purposes within the lung, using inhaled polystyrene nanoparticles loaded with the near-infrared fluorescence dye Itrybe (Itrybe-NPs). By means of in vivo and ex vivo fluorescence reflectance imaging of an ovalbumin-based allergic airway inflammation (AAI) model in hairless SKH-1 mice, we show that subsequent to intranasal application of Itrybe-NPs, AAI lungs display fluorescence intensities significantly higher than those in lungs of control mice for at least 24 h. Ex vivo immunofluorescence analysis of lung tissue demonstrates the uptake of Itrybe-NPs predominantly by CD68(+)CD11c(+)ECF-L(+)MHCII(low) cells, identifying them as alveolar M2 macrophages in the peribronchial and alveolar areas. The in vivo results were validated by confocal microscopy, overlapping tile analysis, and flow cytometry, showing an amount of Itrybe-NP-containing macrophages in lungs of AAI mice significantly larger than that in controls. A small percentage of NP-containing cells were identified as dendritic cells. Flow cytometry of tracheobronchial lymph nodes showed that Itrybe-NPs were negligible in lung draining lymph nodes 24 h after inhalation. This imaging approach may advance preclinical monitoring of AAI in vivo over time and aid the investigation of the role that macrophages play during lung inflammation. Furthermore, it allows for tracking of inhaled nanoparticles and can hence be utilized for studies of the fate of potential new nanotherapeutics.

  13. Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection-Induced Severe Allergic Airway Disease.

    PubMed

    Starkey, Malcolm R; Nguyen, Duc H; Brown, Alexandra C; Essilfie, Ama-Tawiah; Kim, Richard Y; Yagita, Hideo; Horvat, Jay C; Hansbro, Philip M

    2016-04-01

    Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function, and the development of more severe allergic airway disease in later life.

  14. Epidemiology and disease burden from allergic disease in Scotland: analyses of national databases

    PubMed Central

    Anandan, C; Gupta, R; Simpson, CR; Fischbacher, C; Sheikh, A

    2009-01-01

    Summary Background There are ongoing concerns about the quality of care provided to patients with allergic disorders in Scotland, but there are relatively few reliable data on the overall disease burden. We sought to: (1) describe the incidence, prevalence and outcome of allergic disorders; (2) estimate healthcare burden and costs; and (3) investigate ethnic variations in the epidemiology and outcomes from allergic disorders in Scotland. Methods Data sources: national surveys; primary care data; prescribing and medication data; hospital admissions data and mortality data. Results Allergic disorders are extremely common in Scotland, affecting about one in three of the population at some time in their lives. Incidence was highest for eczema (10.2 per 1000 registered patients). Over 4% of all GP consultations and 1.5% of hospital admissions were for allergic disorders. There were 100 asthma deaths in 2005 (20 per million people). Direct healthcare costs for allergic disorders were an estimated £130 million per year, the majority of these being incurred in primary care and related to asthma. Conclusions Allergic disorders are common in Scotland and given the very high proportion of children now affected, the high disease burden associated with these conditions is likely to persist for many decades. PMID:19797601

  15. Occupational and environmental lung disease.

    PubMed

    Seaman, Danielle M; Meyer, Cristopher A; Kanne, Jeffrey P

    2015-06-01

    Occupational and environmental lung disease remains a major cause of respiratory impairment worldwide. Despite regulations, increasing rates of coal worker's pneumoconiosis and progressive massive fibrosis are being reported in the United States. Dust exposures are occurring in new industries, for instance, silica in hydraulic fracking. Nonoccupational environmental lung disease contributes to major respiratory disease, asthma, and COPD. Knowledge of the imaging patterns of occupational and environmental lung disease is critical in diagnosing patients with occult exposures and managing patients with suspected or known exposures.

  16. Occupational and environmental lung disease.

    PubMed

    Seaman, Danielle M; Meyer, Cristopher A; Kanne, Jeffrey P

    2015-06-01

    Occupational and environmental lung disease remains a major cause of respiratory impairment worldwide. Despite regulations, increasing rates of coal worker's pneumoconiosis and progressive massive fibrosis are being reported in the United States. Dust exposures are occurring in new industries, for instance, silica in hydraulic fracking. Nonoccupational environmental lung disease contributes to major respiratory disease, asthma, and COPD. Knowledge of the imaging patterns of occupational and environmental lung disease is critical in diagnosing patients with occult exposures and managing patients with suspected or known exposures. PMID:26024603

  17. Is allergic rhinitis a trivial disease?

    PubMed Central

    Solé, Dirceu; Camelo-Nunes, Inês Cristina; Wandalsen, Gustavo F.; Rosário, Nelson A.; Sarinho, Emanuel C.; ISAAC Group, Brazilian

    2011-01-01

    BACKGROUND: Asthma and rhinitis often coexist, which potentially increases the disease severity and can negatively impact a patients' quality of life. However, there are few reports based on data obtained from the International Study of Asthma and Allergies in Childhood examining asthma severity in combination with rhinitis-related symptoms. OBJECTIVE: To demonstrate whether current rhinitis and current rhinoconjunctivitis are associated with the development of asthma or its increasing severity in Brazilian adolescents. METHODS: The prevalence of current asthma was correlated with the prevalence of current rhinitis and current rhinoconjunctivitis in adolescents (13 to 14 year olds) from 16 Brazilian centers (based on Spearman's rank correlation index). The influence of current rhinitis and current rhinoconjunctivitis on asthma presentation was also evaluated using the chi-squared test and was expressed as odds ratios with 95% confidence intervals (95%CI). RESULTS: A significant positive correlation was observed between the prevalence of current asthma and current rhinitis (rs = 0.82; 95%CI: 0.60–0.93, p<0.0001) and between the prevalence of current asthma and current rhinoconjunctivitis (rs = 0.75; 95%CI: 0.47–0.89, p<0.0001). Current rhinitis was associated with a significantly increased risk of current asthma and of more severe asthma. Similar results were observed for current rhinoconjunctivitis. CONCLUSION: In this epidemiologic study of Brazilian adolescents, the presence of current rhinitis and current rhinoconjunctivitis was associated with a high risk of developing asthma and increased asthma severity. The mutual evaluation of rhinitis and asthma is necessary to establish an adequate treatment plan. PMID:22179162

  18. Air pollution and respiratory allergic diseases in schoolchildren

    PubMed Central

    Nicolussi, Francine Heloisa; dos Santos, Ana Paula Milla; André, Sílvia Carla da Silva; Veiga, Tatiane Bonametti; Takayanagui, Angela Maria Magosso

    2014-01-01

    Study on the prevalence of allergic respiratory diseases in schoolchildren between six and seven years old, associated with indicators of air pollution. A questionnaire based on the International Study of Asthma and Allergies in Childhood was administered to parents of students from public schools, located in urban areas with differing vehicle flows. There was a positive correlation between monthly frequency of rhinitis and concentration of pollutants, and negative with relative air humidity. Even with levels of air pollutants below that allowed by law, the prevalence of asthma, rhinitis and associated symptoms tended to be higher in the central region school, where there is heavy vehicular traffic. PMID:24897055

  19. Primary prevention of allergic disease through nutritional interventions.

    PubMed

    Fleischer, David M; Spergel, Jonathan M; Assa'ad, Amal H; Pongracic, Jacqueline A

    2013-01-01

    With the rising prevalence of atopic disease, primary prevention may play a role in reducing its burden, especially in high-risk infants. With this in mind, the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology was charged with the task of developing recommendations for primary care physicians and specialists about the primary prevention of allergic disease through nutritional interventions according to current available literature and expert opinion. Recommendations that are supported by data are as follows. Avoidance diets during pregnancy and lactation are not recommended at this time, but more research is necessary for peanut. Exclusive breast-feeding for at least 4 and up to 6 months is endorsed. For high-risk infants who cannot be exclusively breast-fed, hydrolyzed formula appears to offer advantages to prevent allergic disease and cow's milk allergy. Complementary foods can be introduced between 4 and 6 months of age. Because no formal recommendations have been previously provided about how and when to introduce the main allergenic foods (cow's milk, egg, soy, wheat, peanut, tree nuts, fish, shellfish), these are now provided, and reasons to consider allergy consultation for development of a personalized plan for food introduction are also presented.

  20. Gastroesophageal reflux and lung disease.

    PubMed

    Meyer, Keith C

    2015-08-01

    Gastroesophageal reflux (GER) can cause respiratory symptoms and may trigger, drive and/or worsen airway disorders, interstitial lung diseases and lung allograft dysfunction. Whether lifestyle changes and acid suppression alone can counter and prevent the adverse effects of GER on the respiratory tract remains unclear. Recent data suggest that antireflux surgery may be more effective in preventing lung disease progression in patients with idiopathic pulmonary fibrosis or lung transplant recipients who have evidence of allograft dysfunction associated with the presence of excessive GER. Additional research and clinical trials are needed to determine the role of GER in various lung disorders and identify which interventions are most efficacious in preventing the respiratory consequences of gastroesophageal reflux disease. In addition, measuring biomarkers that indicate that gastric refluxate has been aspirated into the lower respiratory tract (e.g., pepsin and bile acid concentrations in bronchoalveolar lavage fluid) may prove helpful in both diagnosis and therapeutic decision making.

  1. Interaction of vitamin E isoforms on asthma and allergic airway disease.

    PubMed

    Cook-Mills, Joan; Gebretsadik, Tebeb; Abdala-Valencia, Hiam; Green, Jeremy; Larkin, Emma K; Dupont, William D; Shu, Xiao Ou; Gross, Myron; Bai, Chunxue; Gao, Yu-Tang; Hartman, Terryl J; Rosas-Salazar, Christian; Hartert, Tina

    2016-10-01

    Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease.

  2. Interaction of vitamin E isoforms on asthma and allergic airway disease.

    PubMed

    Cook-Mills, Joan; Gebretsadik, Tebeb; Abdala-Valencia, Hiam; Green, Jeremy; Larkin, Emma K; Dupont, William D; Shu, Xiao Ou; Gross, Myron; Bai, Chunxue; Gao, Yu-Tang; Hartman, Terryl J; Rosas-Salazar, Christian; Hartert, Tina

    2016-10-01

    Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease. PMID:27257004

  3. Acetaminophen Attenuates House Dust Mite-Induced Allergic Airway Disease in Mice.

    PubMed

    Smith, Gregory J; Thrall, Roger S; Cloutier, Michelle M; Manautou, Jose E; Morris, John B

    2016-09-01

    Epidemiologic evidence suggests that N-acetyl-para-aminophenol (APAP) may play a role in the pathogenesis of asthma, likely through pro-oxidant mechanisms. However, no studies have investigated the direct effects of APAP on the development of allergic inflammation. To determine the likelihood of a causal relationship between APAP and asthma pathogenesis, we explored the effects of APAP on inflammatory responses in a murine house dust mite (HDM) model of allergic airway disease. We hypothesized that APAP would enhance the development of HDM-induced allergic inflammation. The HDM model consisted of once daily intranasal instillations for up to 2 weeks with APAP or vehicle administration 1 hour prior to HDM during either week 1 or 2. Primary assessment of inflammation included bronchoalveolar lavage (BAL), cytokine expression in lung tissue, and histopathology. Contrary to our hypothesis, the effects of HDM treatment were substantially diminished in APAP-treated groups compared with controls. APAP-treated groups had markedly reduced airway inflammation: including decreased inflammatory cells in the BAL fluid, lower cytokine expression in lung tissue, and less perivascular and peribronchiolar immune cell infiltration. The anti-inflammatory effect of APAP was not abrogated by an inhibitor of cytochrome P450 (P450) metabolism, suggesting that the effect was due to the parent compound or a non-P450 generated metabolite. Taken together, our studies do not support the biologic plausibility of the APAP hypothesis that APAP use may contribute to the causation of asthma. Importantly, we suggest the mechanism by which APAP modulates airway inflammation may provide novel therapeutic targets for asthma. PMID:27402277

  4. Asthma and Allergic Diseases in Pregnancy: A Review

    PubMed Central

    2009-01-01

    Asthma and allergic disorders can affect the course and outcome of pregnancy. Pregnancy itself may also affect the course of asthma and related diseases. Optimal management of these disorders during pregnancy is vital to ensure the welfare of the mother and the baby. Specific pharmacological agents for treatment of asthma or allergic diseases must be cautiously selected and are discussed here with respect to safety considerations in pregnancy. Although most drugs do not harm the fetus, this knowledge is incomplete. Any drug may carry a small risk that must be balanced against the benefits of keeping the mother and baby healthy. The goals and principles of management for acute and chronic asthma, rhinitis, and dermatologic disorders are the same during pregnancy as those for asthma in the general population. Diagnosis of allergy during pregnancy should mainly consist of the patient's history and in vitro testing. The assured and well-evaluated risk factors revealed for sensitization in mother and child are very limited, to date, and include alcohol consumption, exposure to tobacco smoke, maternal diet and diet of the newborn, drug usage, and insufficient exposure to environmental bacteria. Consequently, the recommendations for primary and secondary preventive measures are also very limited in number and verification. PMID:21151812

  5. Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation

    PubMed Central

    1996-01-01

    We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP- 5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP- 5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation. PMID:8920881

  6. Sex Differences and Sex Steroids in Lung Health and Disease

    PubMed Central

    Townsend, Elizabeth A.; Miller, Virginia M.

    2012-01-01

    Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span. PMID:22240244

  7. Drug Induced Interstitial Lung Disease

    PubMed Central

    Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Märkl, Bruno; Foerg, Wolfgang; Berghaus, Thomas

    2012-01-01

    With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease. PMID:22896776

  8. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases.

    PubMed

    Miyata, Jun; Arita, Makoto

    2015-01-01

    Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are found naturally in fish oil and are commonly thought to be anti-inflammatory nutrients, with protective effects in inflammatory diseases including asthma and allergies. The mechanisms of these effects remain mostly unknown but are of great interest for their potential therapeutic applications. Large numbers of epidemiological and observational studies investigating the effect of fish intake or omega-3 fatty acid supplementation during pregnancy, lactation, infancy, childhood, and adulthood on asthmatic and allergic outcomes have been conducted. They mostly indicate protective effects and suggest a causal relationship between decreased intake of fish oil in modernized diets and an increasing number of individuals with asthma or other allergic diseases. Specialized pro-resolving mediators (SPM: protectins, resolvins, and maresins) are generated from omega-3 fatty acids such as EPA and DHA via several enzymatic reactions. These mediators counter-regulate airway eosinophilic inflammation and promote the resolution of inflammation in vivo. Several reports have indicated that the biosynthesis of SPM is impaired, especially in severe asthma, which suggests that chronic inflammation in the lung might result from a resolution defect. This article focuses on the beneficial aspects of omega-3 fatty acids and offers recent insights into their bioactive metabolites including resolvins and protectins.

  9. Probiotics and lung diseases.

    PubMed

    Forsythe, Paul

    2011-04-01

    Increasing awareness of the role of intestinal commensal bacteria in the development and modulation of the immune system has led to great interest in the therapeutic potential of probiotics and other bacteria-based strategies for a range of immune-related disorders. Studies in animal models have identified strong immunomodulatory effects of many nonpathogenic bacteria and provided evidence that intestinal microbes can activate a common mucosal immune response and, thus, influence sites distant to the intestine, including the respiratory tract. Respiratory effects of probiotics in animal models have included attenuating allergic airway responses and protecting against respiratory pathogens. Dendritic cells appear central to directing the beneficial immune response to probiotic bacteria and in translating microbial signals from the innate to the adaptive immune system, whereas regulatory T cells are emerging as potentially key effectors of probiotic-mediated responses, particularly in the reduction of allergic inflammation. Despite progress in basic research, clinical trials of probiotics in allergy/asthma and respiratory infection have been highly variable at best, leading to an undermining of confidence in this potential therapeutic strategy. It is clear that there is still much to learn regarding the determinants of the diverse immune responses elicited by different bacterial strains. A deeper knowledge of the interactions between administered probiotics and the existing microbiota, together with an understanding of how the dialogue between microbes and the innate immune system is translated into beneficial/protective responses, will be required before we can achieve clinically effective bacteria-based strategies that maintain and promote respiratory health.

  10. Interstitial lung disease in scleroderma.

    PubMed

    Schoenfeld, Sara R; Castelino, Flavia V

    2015-05-01

    Systemic sclerosis is a heterogeneous disease of unknown etiology with limited effective therapies. It is characterized by autoimmunity, vasculopathy, and fibrosis and is clinically manifested by multiorgan involvement. Interstitial lung disease is a common complication of systemic sclerosis and is associated with significant morbidity and mortality. The diagnosis of interstitial lung disease hinges on careful clinical evaluation and pulmonary function tests and high-resolution computed tomography. Effective therapeutic options are still limited. Several experimental therapies are currently in early-phase clinical trials and show promise.

  11. Complement system in lung disease.

    PubMed

    Pandya, Pankita H; Wilkes, David S

    2014-10-01

    In addition to its established contribution to innate immunity, recent studies have suggested novel roles for the complement system in the development of various lung diseases. Several studies have demonstrated that complement may serve as a key link between innate and adaptive immunity in a variety of pulmonary conditions. However, the specific contributions of complement to lung diseases based on innate and adaptive immunity are just beginning to emerge. Elucidating the role of complement-mediated immune regulation in these diseases will help to identify new targets for therapeutic interventions.

  12. [Sensitization to granary mites in patients with allergic diseases].

    PubMed

    Golysheva, M A

    1991-01-01

    As many as 71 patients selected from a group of 550 patients suffering from allergic diseases, sensitized to the house dust mites Dermatophagoides pteronyssinus were examined. A study was made of the presence of allergen-specific IgE antibodies against house dust mites, storage mites (7 species altogether) using allergenic discs and commercial kits RAST (Pharmacia, Sweden). The group under examination mostly manifested sensitization to the house dust mites: Dermatophagoides ferinae (80%), Euroglyphus maynei (55%); storage mites: Acarus siro (45%), Lepidoglyphus destructor (35%). The latter one possesses the most powerful allergenic properties as compared to the acaroid mites of other types. The elevated sensitivity to storage mites is encountered among adults and children living both in Moscow and other regions (urban and rural). The problem of sensitization to storage mites in the USSR mandates thorough studies, which will enable the treatment and diagnostic agents to be designed and introduced into practice.

  13. Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.

    PubMed

    Clayton, Gina M; Wang, Yang; Crawford, Frances; Novikov, Andrey; Wimberly, Brian T; Kieft, Jeffrey S; Falta, Michael T; Bowerman, Natalie A; Marrack, Philippa; Fontenot, Andrew P; Dai, Shaodong; Kappler, John W

    2014-07-01

    T-cell-mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein and self-peptide is unknown. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. Here, we show that the T cell ligand is created when a Be(2+) cation becomes buried in an HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic amino acids. Surprisingly, the TCR does not interact with the Be(2+) itself, but rather with surface changes induced by the firmly bound Be(2+) and an accompanying Na(+) cation. Thus, CBD, by creating a new antigen by indirectly modifying the structure of preexisting self MHC-peptide complex, lies on the border between allergic hypersensitivity and autoimmunity.

  14. Scientists find link between allergic and autoimmune diseases in mouse study

    Cancer.gov

    Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such as multiple sclerosis, asthma, Crohn's disease, ce

  15. Molecular diagnosis in lung diseases.

    PubMed

    Calabrese, Fiorella; Lunardi, Francesca; Popper, Helmut

    2015-01-01

    The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors.

  16. Dietary prevention of allergic diseases in infants and small children.

    PubMed

    Høst, Arne; Halken, Susanne; Muraro, Antonella; Dreborg, Sten; Niggemann, Bodo; Aalberse, Rob; Arshad, Syed H; von Berg, Andrea; Carlsen, Kai-Håkon; Duschén, Karel; Eigenmann, Philippe A; Hill, David; Jones, Catherine; Mellon, Michael; Oldeus, Göran; Oranje, Arnold; Pascual, Cristina; Prescott, Susan; Sampson, Hugh; Svartengren, Magnus; Wahn, Ulrich; Warner, Jill A; Warner, John O; Vandenplas, Yvan; Wickman, Magnus; Zeiger, Robert S

    2008-02-01

    Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.

  17. Evaluation of allergic lung inflammation by computed tomography in a rat model in vivo.

    PubMed

    Jobse, B N; Johnson, J R; Farncombe, T H; Labiris, R; Walker, T D; Goncharova, S; Jordana, M

    2009-06-01

    The ability of micro-computed tomography (CT) to noninvasively evaluate allergic pulmonary inflammation in an experimental model was investigated. In addition, two image segmentation methods and the value of respiratory gating were investigated in the context of this model. Brown Norway rats were exposed to one of four doses of house dust mite (HDM) extract (0, 0.15, 15 or 150 microg) delivered intratracheally every 24 h for 10 days. CT scanning was performed at baseline and after several longitudinal HDM exposures. Both thoracic- and lung-segmentation methods yielded similar results when standardisation practices were employed. While tissue histology correlated well with CT images, cell counts from bronchoalveolar lavage depicted greater inflammation than did density measures from CT images. Evidence from representative CT slices and transaxial density distribution indicated that inflammation was primarily associated with major airways and extended into the periphery from these focal points. Respiratory gating demonstrated that images of the inspiratory state provided greater contrast of inflammatory processes. Lastly, decreases in tidal volumes indicated significant mechanical respiratory changes in animals exposed to both 15 and 150 microg. In summary, CT image segmentation can extract pertinent data on in vivo allergic airway/lung inflammation. Furthermore, respiratory gating provides additional contrast and insight into these quantification practices.

  18. Sleep in patients with restrictive lung disease.

    PubMed

    Won, Christine H J; Kryger, Meir

    2014-09-01

    Restrictive lung disease leads to ventilatory defects and diffusion impairments. These changes may contribute to abnormal nocturnal pathophysiology, including sleep architecture disruption and impaired ventilation and oxygenation. Patients with restrictive lung disease may suffer significant daytime fatigue and dysfunction. Hypercarbia and hypoxemia during sleep may impact progression of lung disease and related symptoms. Little is known about the impact of treatment of sleep disruption on sleep quality and overall prognosis in restrictive lung disease. This review discusses the pathophysiology of sleep and comorbid sleep disorders in restrictive lung diseases including interstitial lung disease, neuromuscular disease, and obesity hypoventilation syndrome.

  19. Impact of perinatal environmental tobacco smoke on the development of childhood allergic diseases

    PubMed Central

    2016-01-01

    Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear. Thus, it is important to identify and control risk factors in the susceptible individual for the best prevention and management. Genetic susceptibility or environments may be a potential background for the development of allergic disease, however they alone cannot explain the rising prevalence worldwide. There is growing evidence that epigenetic change depends on the gene, environment, and their interactions, may induce a long-lasting altered gene expression and the consequent development of allergic diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure during critical period (i.e., during pregnancy and early life) are considered as a potential cause of the development of childhood allergic diseases. However, the causal relationship is still unclear. This review aimed to highlight the impact of ETS exposure during the perinatal period on the development of childhood allergic diseases and to propose a future research direction. PMID:27610180

  20. Impact of perinatal environmental tobacco smoke on the development of childhood allergic diseases.

    PubMed

    Yang, Hyeon-Jong

    2016-08-01

    Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear. Thus, it is important to identify and control risk factors in the susceptible individual for the best prevention and management. Genetic susceptibility or environments may be a potential background for the development of allergic disease, however they alone cannot explain the rising prevalence worldwide. There is growing evidence that epigenetic change depends on the gene, environment, and their interactions, may induce a long-lasting altered gene expression and the consequent development of allergic diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure during critical period (i.e., during pregnancy and early life) are considered as a potential cause of the development of childhood allergic diseases. However, the causal relationship is still unclear. This review aimed to highlight the impact of ETS exposure during the perinatal period on the development of childhood allergic diseases and to propose a future research direction. PMID:27610180

  1. Impact of perinatal environmental tobacco smoke on the development of childhood allergic diseases

    PubMed Central

    2016-01-01

    Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear. Thus, it is important to identify and control risk factors in the susceptible individual for the best prevention and management. Genetic susceptibility or environments may be a potential background for the development of allergic disease, however they alone cannot explain the rising prevalence worldwide. There is growing evidence that epigenetic change depends on the gene, environment, and their interactions, may induce a long-lasting altered gene expression and the consequent development of allergic diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure during critical period (i.e., during pregnancy and early life) are considered as a potential cause of the development of childhood allergic diseases. However, the causal relationship is still unclear. This review aimed to highlight the impact of ETS exposure during the perinatal period on the development of childhood allergic diseases and to propose a future research direction.

  2. Spectrum of fibrosing diffuse parenchymal lung disease.

    PubMed

    Morgenthau, Adam S; Padilla, Maria L

    2009-02-01

    The interstitial lung diseases are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the pulmonary interstitium. In 2002, the American Thoracic Society and the European Respiratory Society revised the classification of interstitial lung diseases and introduced the term diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are a subtype of diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are subdivided into usual interstitial pneumonia (with its clinical counterpart idiopathic interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2 most common granulomatous diffuse parenchymal lung diseases. Rheumatoid arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing antisynthetase syndrome) are diffuse parenchymal lung diseases of known association because these conditions are associated with connective tissue disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lung disease characterized by the clinical triad of pulmonary disease, oculocutaneous albinism, and bleeding diathesis. This review provides an overview of the chronic fibrosing diffuse parenchymal lung diseases. Its primary objective is to illuminate the clinical challenges encountered by clinicians who manage the diffuse parenchymal lung diseases regularly and to offer potential solutions to those challenges. Treatment for the diffuse parenchymal lung diseases is limited, and for many patients with end-stage disease, lung transplantation remains the best option. Although much has been learned about the diffuse parenchymal lung diseases during the past decade, research in these diseases is urgently needed. PMID:19170214

  3. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease. PMID:18160846

  4. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

  5. Evidence for linkage of a new region (11p14) to eczema and allergic diseases

    PubMed Central

    Guilloud-Bataille, Michel; Bouzigon, Emmanuelle; Annesi-Maesano, Isabella; Bousquet, Jean; Charpin, Denis; Gormand, Frédéric; Hochez, Joëlle; Just, Jocelyne; Lemainque, Arnaud; Le Moual, Nicole; Matran, Régis; Neukirch, Françoise; Oryszczyn, Marie-Pierre; Paty, Evelyne; Pin, Isabelle; Vervloet, Daniel; Kauffmann, Francine; Lathrop, Mark; Demenais, Florence; Dizier, Marie-Hélène

    2008-01-01

    SUMMARY Asthma, allergic rhinitis (AR) and atopic dermatitis also called eczema are allergic co-morbidites which are likely to depend on pleiotropic genetic effects as well as on specific genetic factors. After a previous genome-wide linkage screen conducted for asthma and AR in a sample of 295 French EGEA families ascertained through asthmatic subjects, the aim here was to search for genetic factors involved in eczema and more particularly those ones shared by the three allergic diseases using the same EGEA data. In this sake, eczema and phenotypes of ‘allergic disease’ accounting for the joint information on the presence/absence of the three diseases were examined by linkage analyses using the Maximum Likelihood Binomial (MLB) method. A fine mapping was carried out in regions detected for potential linkage, followed by association studies using the Family Based Association Test (FBAT). Evidence for linkage to 11p14 region was shown for ‘allergic disease’ and eczema. Linkage was also indicated between eczema and 5q13 and between ‘allergic disease’ and both 5p15 and 17q21 regions. Fine mapping supported the evidence of linkage to 11p14 and FBAT analyses showed association between ‘allergic disease’ and a marker located at the linkage peak on 11p14. Further investigations in this region will allow identifying genetic factor(s) which could have pleiotropic effect in the three allergic diseases. PMID:17943316

  6. DIESEL PARTICLE INSTILLATION ENHANCES INFLAMMATORY AND NEUROTROPHIN RESPONSES IN THE LUNGS OF ALLERGIC BALB/C MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airways resistance and inflammation. Antibody blockade of NGF attenuates airways resistance associated with the allergen-specific airways responses in mice. ...

  7. Cilia Dysfunction in Lung Disease

    PubMed Central

    Tilley, Ann E.; Walters, Matthew S.; Shaykhiev, Renat; Crystal, Ronald G.

    2015-01-01

    A characteristic feature of the human airway epithelium is the presence of ciliated cells bearing motile cilia, specialized cell surface projections containing axonemes comprised of microtubules and dynein arms, which provide ATP-driven motility. In the airways, cilia function in concert with airway mucus to mediate the critical function of mucociliary clearance, cleansing the airways of inhaled particles and pathogens. The prototypical disorder of respiratory cilia is primary ciliary dyskinesia, an inherited disorder that leads to impaired mucociliary clearance, repeated chest infections, and progressive destruction of lung architecture. Numerous acquired lung diseases are also marked by abnormalities in both cilia structure and function. In this review we summarize current knowledge regarding airway ciliated cells and cilia, how they function to maintain a healthy epithelium, and how disorders of cilia structure and function contribute to inherited and acquired lung disease. PMID:25386990

  8. Climate change, air pollution and extreme events leading to increasing prevalence of allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro; Baena-Cagnani, Carlos E; Cecchi, Lorenzo; Annesi-Maesano, Isabella; Nunes, Carlos; Ansotegui, Ignacio; D'Amato, Maria; Liccardi, Gennaro; Sofia, Matteo; Canonica, Walter G

    2013-01-01

    The prevalence of asthma and allergic diseases has increased dramatically during the past few decades not only in industrialized countries. Urban air pollution from motor vehicles has been indicated as one of the major risk factors responsible for this increase.Although genetic factors are important in the development of asthma and allergic diseases, the rising trend can be explained only in changes occurred in the environment. Despite some differences in the air pollution profile and decreasing trends of some key air pollutants, air quality is an important concern for public health in the cities throughout the world.Due to climate change, air pollution patterns are changing in several urbanized areas of the world, with a significant effect on respiratory health.The observational evidence indicates that recent regional changes in climate, particularly temperature increases, have already affected a diverse set of physical and biological systems in many parts of the world. Associations between thunderstorms and asthma morbidity in pollinosis subjects have been also identified in multiple locations around the world.Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollens especially in presence of specific weather conditions.The underlying mechanisms of all these interactions are not well known yet. The consequences on health vary from decreases in lung function to allergic diseases, new onset of diseases, and exacerbation of chronic respiratory diseases.Factor clouding the issue is that laboratory evaluations do not reflect what happens during natural exposition, when atmospheric pollution mixtures in polluted cities are inhaled. In addition, it is important to recall that an individual's response to pollution exposure depends on the source and components of air pollution, as well as meteorological conditions. Indeed, some air pollution-related incidents with asthma aggravation do not depend

  9. Climate change, air pollution and extreme events leading to increasing prevalence of allergic respiratory diseases

    PubMed Central

    2013-01-01

    The prevalence of asthma and allergic diseases has increased dramatically during the past few decades not only in industrialized countries. Urban air pollution from motor vehicles has been indicated as one of the major risk factors responsible for this increase. Although genetic factors are important in the development of asthma and allergic diseases, the rising trend can be explained only in changes occurred in the environment. Despite some differences in the air pollution profile and decreasing trends of some key air pollutants, air quality is an important concern for public health in the cities throughout the world. Due to climate change, air pollution patterns are changing in several urbanized areas of the world, with a significant effect on respiratory health. The observational evidence indicates that recent regional changes in climate, particularly temperature increases, have already affected a diverse set of physical and biological systems in many parts of the world. Associations between thunderstorms and asthma morbidity in pollinosis subjects have been also identified in multiple locations around the world. Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollens especially in presence of specific weather conditions. The underlying mechanisms of all these interactions are not well known yet. The consequences on health vary from decreases in lung function to allergic diseases, new onset of diseases, and exacerbation of chronic respiratory diseases. Factor clouding the issue is that laboratory evaluations do not reflect what happens during natural exposition, when atmospheric pollution mixtures in polluted cities are inhaled. In addition, it is important to recall that an individual’s response to pollution exposure depends on the source and components of air pollution, as well as meteorological conditions. Indeed, some air pollution-related incidents with asthma aggravation do not

  10. Climate change, air pollution and extreme events leading to increasing prevalence of allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro; Baena-Cagnani, Carlos E; Cecchi, Lorenzo; Annesi-Maesano, Isabella; Nunes, Carlos; Ansotegui, Ignacio; D'Amato, Maria; Liccardi, Gennaro; Sofia, Matteo; Canonica, Walter G

    2013-02-11

    The prevalence of asthma and allergic diseases has increased dramatically during the past few decades not only in industrialized countries. Urban air pollution from motor vehicles has been indicated as one of the major risk factors responsible for this increase.Although genetic factors are important in the development of asthma and allergic diseases, the rising trend can be explained only in changes occurred in the environment. Despite some differences in the air pollution profile and decreasing trends of some key air pollutants, air quality is an important concern for public health in the cities throughout the world.Due to climate change, air pollution patterns are changing in several urbanized areas of the world, with a significant effect on respiratory health.The observational evidence indicates that recent regional changes in climate, particularly temperature increases, have already affected a diverse set of physical and biological systems in many parts of the world. Associations between thunderstorms and asthma morbidity in pollinosis subjects have been also identified in multiple locations around the world.Allergens patterns are also changing in response to climate change and air pollution can modify the allergenic potential of pollens especially in presence of specific weather conditions.The underlying mechanisms of all these interactions are not well known yet. The consequences on health vary from decreases in lung function to allergic diseases, new onset of diseases, and exacerbation of chronic respiratory diseases.Factor clouding the issue is that laboratory evaluations do not reflect what happens during natural exposition, when atmospheric pollution mixtures in polluted cities are inhaled. In addition, it is important to recall that an individual's response to pollution exposure depends on the source and components of air pollution, as well as meteorological conditions. Indeed, some air pollution-related incidents with asthma aggravation do not depend

  11. CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy

    SciTech Connect

    Niimi, Hiroshi; Kang, Eun-Young; Kwong, S.

    1996-03-01

    Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodes (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.

  12. Flavorings-Related Lung Disease

    MedlinePlus

    ... message, please visit this page: About CDC.gov . Workplace Safety & Health Topics Flavorings-Related Lung Disease Exposures to ... Pinterest Twitter YouTube NIOSH Homepage NIOSH A-Z Workplace Safety & Health Topics Publications and Products Programs Contact NIOSH ...

  13. Systems Biology of Asthma and Allergic Diseases: A Multiscale Approach

    PubMed Central

    Bunyavanich, Supinda; Schadt, Eric E.

    2014-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article, we review the technologies and approaches for system-wide profiling as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually-captured health profiles will contribute to more accurate systems biology views of asthma and allergy. PMID:25468194

  14. Systems biology of asthma and allergic diseases: a multiscale approach.

    PubMed

    Bunyavanich, Supinda; Schadt, Eric E

    2015-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High-throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article we review the technologies and approaches for system-wide profiling, as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually captured health profiles will contribute to more accurate systems biology views of asthma and allergy.

  15. A novel microbe-based treatment that attenuates the inflammatory profile in a mouse model of allergic airway disease

    PubMed Central

    Bazett, Mark; Biala, Agnieszka; Huff, Ryan D.; Bosiljcic, Momir; Gunn, Hal; Kalyan, Shirin; Hirota, Jeremy A.

    2016-01-01

    There is an unmet need for effective new and innovative treatments for asthma. It is becoming increasingly evident that bacterial stimulation can have beneficial effects at attenuating allergic airway disease through immune modulation. Our aim was to test the ability of a novel inactivated microbe-derived therapeutic based on Klebsiella (KB) in a model of allergic airway disease in mice. BALB/c mice were exposed intranasally to house dust mite (HDM) for two weeks. Mice were treated prophylactically via subcutaneous route with either KB or placebo for one week prior to HDM exposure and throughout the two week exposure period. 24 hours after the last exposure, lungs were analysed for inflammatory cell infiltrate, gene expression, cytokine levels, goblet cell metaplasia, and serum was analysed for allergen-specific serum IgE levels. HDM exposed mice developed goblet cell hyperplasia, elevated allergen-specific serum IgE, airway eosinophilia, and a concomitant increase in TH2 cytokines including IL-4, IL-13 and IL-5. Treatment with KB attenuated HDM-mediated airway eosinophilia, total bronchoalveolar lavage (BAL) cell numbers, BAL TH2 cytokine production, and goblet cell metaplasia. Our prophylactic intervention study illustrates the potential of subcutaneous treatment with bacterial derived biologics as a promising approach for allergic airway disease treatment. PMID:27734946

  16. Rare Lung Diseases: Interstitial Lung Diseases and Lung Manifestations of Rheumatological Diseases.

    PubMed

    Ramamurthy, Mahesh Babu; Goh, Daniel Y T; Lim, Michael Teik Chung

    2015-10-01

    The concept of Childhood Interstitial Lung Disease (ChILD) is relatively young. There has been tremendous progress in this field in the last decade. The key advance has been the recognition of interstitial lung diseases that are often distinct and occur mainly in infants. Diagnosis is challenging because the incidence is low and no single center in the world has enough cases to promote experience and clinical skills. This has led to formation of international groups of people interested in the field and the "Children's interstitial and diffuse lung disease research network" (ChILDRN) is one such group which contributed to the progress of this field. Clinically, these disorders overlap with those of other common respiratory disorders. Hence, clinical practice guidelines emphasize the additional role of chest imaging, genetic testing and lung biopsy in the diagnostic evaluation. Genetic testing, in particular, has shown tremendous progress in this field. Being noninvasive, it has the potential to help early recognition in a vast majority. Despite progress, definitive therapeutic modalities are still lacking and supportive care is still the backbone of management in the majority. Early recognition of the definitive diagnosis helps in the management, even if, in a significant number, it helps in avoiding unnecessary therapy. Also discussed in this article, is the pulmonary manifestation of rheumatic diseases in children. The incidence and spectrum of pulmonary involvement in rheumatic conditions vary and can be result of the primary disease or its management or due to an concurrent infection. PMID:26286176

  17. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor

    PubMed Central

    Malmhäll, Carina; Rådinger, Madeleine; Ramos-Ramirez, Patricia; Lu, You; Deák, Tünde; Semitekolou, Maria; Gaga, Mina; Sjöstrand, Margareta; Lötvall, Jan; Bossios, Apostolos

    2016-01-01

    Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. Methods A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Results Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Conclusion Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation. PMID:27513955

  18. BN 52021 (a platelet activating factor-receptor antagonist) decreases alveolar macrophage-mediated lung injury in experimental extrinsic allergic alveolitis.

    PubMed Central

    Pérez-Arellano, J L; Martín, T; López-Novoa, J M; Sánchez, M L; Montero, A; Jiménez, A

    1998-01-01

    Several lines of research indirectly suggest that platelet activating factor (PAF) may intervene in the pathogenesis of extrinsic allergic alveolitis (EAA). The specific aim of our study was to evaluate the participation of PAF on macrophage activation during the acute phase of EAA in an experimental model of this disease developed in guinea pigs. Initially we measured the concentration of PAF in bronchoalvedar lavage fluid, blood and lung tissue. In a second phase we evaluate the participation of PAF on alveolar macrophage activation and parenchymal lung injury. The effect of PAF on parenchymal lung injury was evaluated by measuring several lung parenchymatous lesion indices (lung index, bronchoalvedar lavage fluid (BALF) lactic hydrogenase activity and BALF alkaline phosphatase activity) and parameters of systemic response to the challenge (acute phase reagents). We observed that induction of the experimental EAA gave rise to an increase in the concentration of PAF in blood and in lung tissue. The use of the PAF-receptor antagonist BN52021 decreases the release of lysosomal enzymes (beta-glucuronidase and tartrate-sensitive acid phosphatase) to the extracellular environment both in vivo and in vitro. Furthermore, antagonism of the PAF receptors notably decreases pulmonary parenchymatous lesion. These data suggest that lung lesions from acute EAA are partly mediated by local production of PAF. PMID:9705608

  19. The Treatment of Allergic Respiratory Disease During Pregnancy.

    PubMed

    Namazy, Jai; Schatz, M

    2016-01-01

    Pregnancy may be complicated by new-onset or preexisting asthma and allergic rhinitis.This article reviews the recognition and management of asthma and allergic rhinitis during pregnancy, paying close attention to the general principles of allergy and use of asthma medication during pregnancy. Both allergic rhinitis and asthma can adversely affect both maternal quality of life and, in the case of maternal asthma, perinatal outcomes. Optimal management is thus important for both mother and baby. This article reviews the safety of asthma and allergy medications commonly used during pregnancy.

  20. Complete right lung agenesis presenting with bronchial asthma and allergic rhinitis.

    PubMed

    Kushwaha, Ram Avadh Singh; Ranganath, T G; Garg, Rajiv; Anand, Shipra

    2012-01-01

    A 26 year-old lady presented with episodic breathlessness, chest tightness, recurrent nasal obstruction and excessive sneezing, mainly during change of season along with opacity of the right hemithorax on chest x-ray. Further detailed work-up including spirometry, high-resolution CT scan of the thorax and fibre-optic bronchoscopy confirmed complete right lung agenesis in patients with bronchial asthma and allergic rhinitis. Complete control of symptoms was achieved with formeterol 6 μg and mometasone 200 μg (via dry powder inhaler) and intranasal fluticasone 50 μg (nasal spray) 2 puffs twice daily and oral montelukast 10 mg with levocetirizine 5 mg once daily. PMID:23001088

  1. Diet and obstructive lung diseases.

    PubMed

    Romieu, I; Trenga, C

    2001-01-01

    The results presented in this review suggest that the impact of nutrition on obstructive lung disease is most evident for antioxidant vitamins, particularly vitamin C and, to a lesser extent, vitamin E. By decreasing oxidant insults to the lung, antioxidants could modulate the development of chronic lung diseases and lung function decrement. Antioxidant vitamins could also play an important role in gene-environment interactions in complex lung diseases such as childhood asthma. Data also suggest that omega-3 fatty acids may have a potentially protective effect against airway hyperreactivity and lung function decrements; however, relevant data are still sparse. Although epidemiologic data suggest that consumption of fresh fruit may reduce risk of noncarcinogenic airway limitation, there are no clear data on which nutrients might be most relevant. While some studies evaluate daily intake of vitamin C, other studies use fruit consumption as a surrogate for antioxidant intake. Given the dietary intercorrelations among antioxidant vitamins, particularly vitamin C, beta-carotene, and flavonoids, as well as other micronutrients, it may be difficult to isolate a specific effect. Some population subgroups with higher levels of oxidative stress, such as cigarette smokers, may be more likely to benefit from dietary supplementation, since some studies have suggested that antioxidant intake may have a greater impact in this group. Studies of lung function decrement and COPD in adults suggest that daily intake of vitamin C at levels slightly exceeding the current Recommended Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among smokers) may have a protective effect (20). In the Schwartz and Weiss (85) and Britton et al. (87) studies, an increase of 40 mg/day in vitamin C intake led to an approximate 20-ml increase in FEV1. Daily mean vitamin C intakes in these studies were 66 mg and 99.2 mg, respectively, and the highest intake level (178 mg/day) was approximately

  2. Maternal PUFA status and offspring allergic diseases up to the age of 18 months.

    PubMed

    Yu, Ya-Mei; Chan, Yiong-Huak; Calder, Philip C; Hardjojo, Antony; Soh, Shu-E; Lim, Ai Lin; Fisk, Helena L; Teoh, Oon Hoe; Goh, Anne; Saw, Seang-Mei; Kwek, Kenneth; Gluckman, Peter D; Godfrey, Keith M; Chong, Yap-Seng; Shek, Lynette Pei-Chi; Pan, An; Chong, Mary Foong Fong; van Bever, Hugo P S

    2015-03-28

    Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother-offspring cohort were assayed at 26-28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.

  3. Adenocarcinoma of Lung Presenting as Interstitial Lung Disease.

    PubMed

    Mohapatra, Prasanta R; Aggarwal, Deepak; Punia, Rajpal S; Janmeja, Ashok K

    2015-01-01

    Interstitial lung diseases (ILDs) presenting as lung cancer have been reported rarely from India. The present case describes a possibly primary lung cancer in a non-smoker who presented radiologically as a case of ILD. The possible mechanisms available in the literature are discussed.

  4. Neonatal Streptococcus pneumoniae Infection May Aggravate Adulthood Allergic Airways Disease in Association with IL-17A

    PubMed Central

    Yang, Ting; Jiang, Xiaoli; Zhang, Liqun; Wang, Lijia; Wang, Qinghong; Luo, Zhengxiu; Liu, Enmei; Fu, Zhou

    2015-01-01

    Epidemiologic studies have demonstrated that some bacteria colonization or infections in early-life increased the risk for subsequent asthma development. However, little is known about the mechanisms by which early-life bacterial infection increases this risk. The aim of this study was to investigate the effect of neonatal Streptococcus pneumoniae infection on the development of adulthood asthma, and to explore the possible mechanism. A non-lethal S. pneumoniae lung infection was established by intranasal inoculation of neonatal (1-week-old) female mice with D39. Mice were sensitized and challenged with ovalbumin in adulthood to induce allergic airways disease (AAD). Twenty-four hours later, the lungs and bronchoalveolar lavage fluid (BALF) were collected to assess AAD. Neonatal S. pneumoniae infection exacerbated adulthood hallmark features of AAD, with enhanced airway hyperresponsiveness and increased neutrophil recruitment into the airways, increased Th17 cells and interleukin (IL)-17A productions. Depletion of IL-17A by i.p. injection of a neutralizing monoclonal antibody reduced neutrophil recruitment into the airways, alleviated airway inflammation and decreased airway hyperresponsiveness. Furthermore, IL-17A depletion partially restored levels of inteferon-γ, but had no effect on the release of IL-5 or IL-13. Our data suggest that neonatal S. pneumoniae infection may promote the development of adulthood asthma in association with increased IL-17A production. PMID:25816135

  5. [Role of fractalkine/CX3CL1 and its receptor CX3CR1 in allergic diseases].

    PubMed

    Julia, Valérie; Staumont-Salle, Delphine; Dombrowicz, David

    2016-03-01

    Allergic asthma and atopic dermatitis are diseases mainly resulting from the activation of Th2 cells, that produce cytokines favouring IgE production and eosinophilia but also of Th1 cells, that contribute to inflammation chronicity. Lymphocyte recruitment and retention of Th cells in target organs are 2 key events for asthma and atopic dermatitis pathogenesis. While lymphocyte migration is regulated by chemokines and lipid mediators such as leukotrienes and prostaglandins, factors involved in lymphocyte retention and survival within inflammatory tissues remain poorly understood. Recent works show that, in allergic diseases, there is an increased expression of fractalkine/CX3CL1 and its unique receptor CX3CR1 and that this chemokine does not act as chemoattractant. In allergic asthma, CX3CR1 expression regulates Th2 and Th1 cell survival in the inflammatory lung, while, in atopic dermatitis, it regulate Th2 and Th1 cell retention into the inflammatory site. Use of peptides blocking fractalkine binding to its receptor is currently tested in the treatment of asthma and atopic dermatitis.

  6. [Recommendations for the management of the child with allergic diseases at school].

    PubMed

    Saranz, Ricardo J; Lozano, Alejandro; Mariño, Andrea; Boudet, Raúl V; Sarraquigne, María Paula; Cáceres, María Elena; Bandín, Gloria; Lukin, Alicia; Skrie, Víctor; Cassaniti, María Cristina; Agüero, Claudio; Chorny, Marta; Reichbach, Débora S; Arnolt, Roque Gustavo; Cavallo, Aldo

    2015-06-01

    Allergic diseases cause great impact on the health related quality of life in children and adolescents, resulting in increased school absenteeism and deficiencies in school performance. Although the bibliographic framework on allergic diseases is wide, in our country, there are no guidelines for proper management of the allergic child at school. It is necessary to establish guidelines for coordinated action among the educational community, the families, the pediatrician, the health team and governmental and non-governmental authorities. This position paper aims to provide information about the impact of allergic diseases on school activities, establish standards of competence of the various stakeholders at school and consider the legal framework for the intervention of the school staff about the child with allergies at school. PMID:25996328

  7. Cough in interstitial lung disease.

    PubMed

    Garner, Justin; George, Peter M; Renzoni, Elisabetta

    2015-12-01

    Cough in the context of interstitial lung disease (ILD) has not been the focus of many studies. However, chronic cough has a major impact on quality of life in a significant proportion of patients with ILD. For the purpose of this review, we have chosen to highlight some of the more frequently encountered diffuse lung diseases including idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis and systemic sclerosis associated ILD. Many of the underlying mechanisms remain speculative and further research is now required to elucidate the complex pathways involved in the pathogenesis of chronic cough in ILD. This will hopefully pave the way for the identification of new therapeutic agents to alleviate this distressing and often intractable symptom.

  8. Gene therapy for lung disease.

    PubMed

    Ennist, D L

    1999-06-01

    Gene therapy is a new field of medical research that has great potential to influence the course of treatment of human disease. The lung has been a particularly attractive target organ for gene therapy due to its accessibility and the identification of genetic deficits for a number of lung diseases. Several clinical trials have shown evidence of low levels of gene transfer and expression, but without any benefit to the patients involved. Thus, current studies are focusing on further research and technological improvements to the vectors. Gene therapy is now beginning to benefit from a shift in emphasis from clinical trials to the development of better tools and procedures to deliver gene therapy to the bedside.

  9. Agricultural lung diseases.

    PubMed Central

    Kirkhorn, S R; Garry, V F

    2000-01-01

    Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gases constitute some of the most common and potentially disabling occupational and environmental hazards. The changing patterns of agriculture have paradoxically contributed to both improved working conditions and increased exposure to respiratory hazards. Animal confinement operations with increasing animal density, particularly swine confinement, have contributed significantly to increased intensity and duration of exposure to indoor air toxins. Ongoing research has implicated bacterial endotoxins, fungal spores, and the inherent toxicity of grain dusts as causes of upper and lower airway inflammation and as immunologic agents in both grain and animal production. Animal confinement gases, particularly ammonia and hydrogen sulfide, have been implicated as additional sources of respiratory irritants. It has become evident that a significant percentage of agricultural workers have clinical symptoms associated with long-term exposure to organic dusts and animal confinement gases. Respiratory diseases and syndromes, including hypersensitivity pneumonitis, organic dust toxic syndrome, chronic bronchitis, mucous membrane inflammation syndrome, and asthmalike syndrome, result from ongoing acute and chronic exposures. In this review we focus upon the emerging respiratory health issues in a changing agricultural economic and technologic environment. Environmental and occupational hazards and exposures will be emphasized rather than clinical diagnosis and treatment. Methods of prevention, from both engineering controls and personal respiratory perspectives, are also addressed. PMID:10931789

  10. Effect of Traffic-Related Air Pollution on Allergic Disease: Results of the Children's Health and Environmental Research

    PubMed Central

    Jung, Dal-Young; Kim, Hwan-Cheol; Kim, Jeong-Hee; Hwang, Seung-Sik; Lee, Ji-Young; Kim, Byoung-Ju; Hong, Yun-Chul; Hong, Soo-Jong; Kwon, Ho-Jang

    2015-01-01

    Purpose This study evaluated the relationship of living near to main roads to allergic diseases, airway hyperresponsiveness (AHR), allergic sensitization, and lung function in Korean children. Methods A total of 5,443 children aged 6-14 years from 33 elementary schools in 10 cities during 2005-2006 were included in a baseline survey of the Children's Health and Environmental Research. We assessed association of traffic-related air pollution (TAP) exposure with the distance to the nearest main road, total road length of main roads and the proportion of the main road area within the 200-m home area. Results Positive exposure-response relationships were found between the length of the main road within the 200-m home area and lifetime wheeze (adjusted prevalence ratio [PR] for comparison of the longest to the shortest length categories=1.24; 95% CIs, 1.04-1.47; P for trend=0.022) and diagnosed asthma (PR=1.42; 95% CIs, 1.08-1.86; P for trend=0.011). Living less than 75 m from the main road was significantly associated with lifetime allergic rhinitis (AR), past-year AR symptoms, diagnosed AR, and treated AR. The distance to the main road (P for trend=0.001), the length of the main road (P for trend=0.041), and the proportion of the main road area (P for trend=0.006) had an exposure-response relationship with allergic sensitization. A strong inverse association was observed between residential proximity to the main load and lung function, especially FEV1, FEV1/FVC, and FEF25-75. The length of the main road and the proportion of the main road area were associated with reduced FEV1 in schoolchildren. Conclusions The results of this study suggest that exposure to traffic-related air pollution may be associated with increased risk of asthma, AR, and allergic sensitization, and with reduced lung function in schoolchildren. PMID:25936911

  11. The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods

    PubMed Central

    2014-01-01

    Background This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. Methods/Design The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim. The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre

  12. Farmer's Lung Disease. A Review.

    PubMed

    Cano-Jiménez, Esteban; Acuña, Adelaida; Botana, María Isabel; Hermida, Teresa; González, María Guadalupe; Leiro, Virginia; Martín, Irene; Paredes, Sonia; Sanjuán, Pilar

    2016-06-01

    Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality.

  13. Farmer's Lung Disease. A Review.

    PubMed

    Cano-Jiménez, Esteban; Acuña, Adelaida; Botana, María Isabel; Hermida, Teresa; González, María Guadalupe; Leiro, Virginia; Martín, Irene; Paredes, Sonia; Sanjuán, Pilar

    2016-06-01

    Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality. PMID:26874898

  14. [Recent advances in DNA vaccines against allergic airway disease: a review].

    PubMed

    Ou, Jin; Xu, Yu; Shi, Wendan

    2013-12-01

    DNA vaccine is used in infectious diseases initially, and later is applied in neoplastic diseases, allergic diseases and other fields with the further understanding of DNA vaccine and the development of genetic engineering. DNA vaccine transfers the genes encoding exogenous antigens to plasmid vector and then is introduced into organism. It controls the antigen proteins synthesis, thus induces specific humoral and cellular immune responses. So it has a broad application prospect in allergic diseases. Compared with the traditional protein vaccines used in specific immunotherapy, DNA vaccine has many advantages, including high purity and specificity, and improvement of patients' compliance etc. However, there are still two unsolved problems. First, the transfection rate of unmodified naked DNA plasmid is not high, Second, it's difficult to induce ideal immune response. In this study, we will review the progress of DNA vaccine applications in respiratory allergic diseases and its various optimization strategies.

  15. ALLERGIC POTENTIAL OF INDOOR MOLDS

    EPA Science Inventory

    Many fungi have been associated with allergic lung disease, but few are well studied and even fewer allergens of fungal origin are well characterized. Exposure to damp moldy environments has been associated with the exacerbation of asthma, but the role of molds in the induction o...

  16. Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

    PubMed

    Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

    2014-12-01

    Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P <0.001) and in diseased cats compared with healthy cats (P <0.02). Bacterial population was significantly higher in allergic cats than in healthy cats (P <0.001) and cats suffering from systemic disease (P <0.001). Bacterial overgrowth was also higher in cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity.

  17. Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

    PubMed

    Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

    2014-12-01

    Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P <0.001) and in diseased cats compared with healthy cats (P <0.02). Bacterial population was significantly higher in allergic cats than in healthy cats (P <0.001) and cats suffering from systemic disease (P <0.001). Bacterial overgrowth was also higher in cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity. PMID:24509255

  18. Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases.

    PubMed

    Sabolić Pipinić, I; Varnai, V M; Turk, R; Breljak, D; Kezić, S; Macan, J

    2013-06-01

    Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing north-south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.

  19. Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice.

    PubMed

    Liu, Cong-Lin; Wang, Yi; Liao, Mengyang; Santos, Marcela M; Fernandes, Cleverson; Sukhova, Galina K; Zhang, Jin-Ying; Cheng, Xiang; Yang, Chongzhe; Huang, Xiaozhu; Levy, Bruce; Libby, Peter; Wu, Gongxiong; Shi, Guo-Ping

    2016-05-01

    Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe(-/-)) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4(+) T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Antiasthmatic medication can efficiently mitigate atherosclerotic lesion pathology.

  20. Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice.

    PubMed

    Liu, Cong-Lin; Wang, Yi; Liao, Mengyang; Santos, Marcela M; Fernandes, Cleverson; Sukhova, Galina K; Zhang, Jin-Ying; Cheng, Xiang; Yang, Chongzhe; Huang, Xiaozhu; Levy, Bruce; Libby, Peter; Wu, Gongxiong; Shi, Guo-Ping

    2016-05-01

    Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe(-/-)) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4(+) T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Antiasthmatic medication can efficiently mitigate atherosclerotic lesion pathology. PMID:26898714

  1. Lung Disease at High Altitude

    PubMed Central

    Stream, JO; Luks, AM; Grissom, CK

    2016-01-01

    Large numbers of people travel to high altitudes, entering an environment of hypobaric hypoxia. Exposure to low oxygen tension leads to a series of important physiologic responses that allow individuals to tolerate these hypoxic conditions. However, in some cases hypoxia triggers maladaptive responses that lead to various forms of acute and chronic high altitude illness, such as high-altitude pulmonary edema or chronic mountain sickness. Because the respiratory system plays a critical role in these adaptive and maladaptive responses, patients with underlying lung disease may be at increased risk for complications in this environment and warrant careful evaluation before any planned sojourn to higher altitudes. In this review, we describe respiratory disorders that occur with both acute and chronic exposures to high altitudes. These disorders may occur in any individual who ascends to high altitude, regardless of his/her baseline pulmonary status. We then consider the safety of high-altitude travel in patients with various forms of underlying lung disease. The available data regarding how these patients fare in hypoxic conditions are reviewed, and recommendations are provided for management prior to and during the planned sojourn. PMID:20477353

  2. The spectrum of allergic fungal diseases of the upper and lower airways.

    PubMed

    Rodrigues, Jonathan; Caruthers, Carrie; Azmeh, Roua; Dykewicz, Mark S; Slavin, Raymond G; Knutsen, Alan P

    2016-01-01

    Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease. PMID:26776889

  3. Pulmonary nuclear medicine: Techniques in diagnosis of lung disease

    SciTech Connect

    Atkins, H.L.

    1984-01-01

    This book presents papers on the application of nuclear medicine to the diagnosis of lung diseases. Topics considered include lung physiology and anatomy, radiopharmaceuticals in pulmonary medicine, pulmonary embolism, obstructive pulmonary disease, diffuse infiltrative lung disease, pneumoconioses, tumor localization scans in primary lung tumors, the interactions of heart diseases and lung diseases on radionuclide tests of lung anatomy and function, radionuclide imaging in pediatric lung diseases, and future possibilities in pulmonary nuclear medicine.

  4. Fexofenadine hydrochloride in the treatment of allergic disease: a review

    PubMed Central

    Axelrod, David; Bielory, Leonard

    2008-01-01

    Fexofenadine is a selective, non-sedating H1 receptor antagonist, marketed in the United States since 2000. The FDA approved an oral suspension in 2006, for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria in children. The tablet, capsule, and oral suspension are bioequivalent. Although fexofenadine does not use P450 CYP 3A4 it does interact with a number of drugs at P-glycoprotein and organic anion transporter polypeptides. The risk of toxicity from other drugs may increase with the administration of fexofenadine. Orange and grapefruit juices reduce the bioavailability of fexofenadine. Fexofenadine has been shown to have an impact on inflammatory mediators, other than histamine, such as decreasing the production of LTC4, LTD4, LTE4, PGE2, and PGF2α; inhibiting cyclo-oxygenase 2, thromboxane; limiting iNOS generation of NO; decreasing cytokine levels (ICAM-1, ELAM-1, VCAM-1, RANTES, I-TAC, MDC, TARC, MMP-2, MMP-9, tryptase); and diminishing eosinophil adherence, chemotaxis, and opsonization of particles. These effects may provide benefit to some of the inflammatory responses of an acute allergic reaction and provide a basis for future development of H1 antagonists with stronger anti-inflammatory effects. These studies also support the contention that fexofenadine is effective for the treatment of allergic rhinits and chronic idiopathic urticaria. PMID:21436982

  5. METALS, PARTICLES AND IMPACT UPON PULMONARY ALLERGIC RESPONSES

    EPA Science Inventory


    The increase in allergic asthma over the past few decades has prompted investigations into whether air pollution may affect either the incidence or severity of allergic lung disease. Population studies have demonstrated that as air pollution rises, symptoms, medication use a...

  6. Omega-6 and omega-3 polyunsaturated fatty acids and allergic diseases in infancy and childhood.

    PubMed

    Miles, Elizabeth A; Calder, Philip C

    2014-01-01

    There may be a causal relationship between intake of n-6 polyunsaturated fatty acids (PUFAs) and childhood allergic diseases. This can be explained by plausible biological mechanisms involving eicosanoid mediators produced from the n-6 PUFA arachidonic acid. Long chain n-3 PUFAs are found in fish and fish oils. These fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will lower the risk of developing allergic diseases. In support of this, protective associations have been reported between maternal fish intake during pregnancy and allergic outcomes in infants and children from those pregnancies. However, studies of fish intake during infancy and childhood and allergic outcomes in those infants or children are inconsistent, although some reported a protective association. Supplementing pregnant women with fish oil can induce immunologic changes in cord blood. This supplementation has been reported in some studies to decrease sensitisation to common food allergens and to lower the prevalence and severity of atopic dermatitis in the first year of life. The protective effect of maternal n-3 PUFAs may last until adolescence of the offspring. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, although this benefit may not persist. Whether fish oil is a useful therapy in children with asthma receiving standard therapy is not clear from studies performed to date and this requires further exploration.

  7. A Case of IgG4-Related Lung Disease Presenting as Interstitial Lung Disease.

    PubMed

    Ahn, Jee Hwan; Hong, Sun In; Cho, Dong Hui; Chae, Eun Jin; Song, Joon Seon; Song, Jin Woo

    2014-08-01

    Intrathoracic involvement of immunoglobulin G4 (IgG4)-related disease has recently been reported. However, a subset of the disease presenting as interstitial lung disease is rare. Here, we report a case of a 35-year-old man with IgG4-related lung disease with manifestations similar to those of interstitial lung disease. Chest computed tomography showed diffuse ground glass opacities and rapidly progressive pleural and subpleural fibrosis in both upper lobes. Histological findings showed diffuse interstitial lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. Serum levels of IgG and IgG4 were also increased. The patient was diagnosed with IgG4-related lung disease, treated with anti-inflammatory agents, and showed improvement. Lung involvement of IgG4-related disease can present as interstitial lung disease and, therefore, should be differentiated when evaluating interstitial lung disease.

  8. Gut Microbiome and the Development of Food Allergy and Allergic Disease.

    PubMed

    Prince, Benjamin T; Mandel, Mark J; Nadeau, Kari; Singh, Anne Marie

    2015-12-01

    The impact of gut microbiome on human development, nutritional needs, and disease has become evident with advances in the ability to study these complex communities of microorganisms, and there is growing appreciation for the role of the microbiome in immune regulation. Several studies have examined associations between changes in the commensal microbiota and the development of asthma, allergic rhinitis, and asthma, but far less have evaluated the impact of the microbiome on the development of food allergy. This article reviews the human gastrointestinal microbiome, focusing on the theory and evidence for its role in the development of IgE-mediated food allergy and other allergic diseases.

  9. Facts and promises on lung biomarkers in interstitial lung diseases.

    PubMed

    Campo, Ilaria; Zorzetto, Michele; Bonella, Francesco

    2015-08-01

    Interstitial lung diseases (ILDs) are a heterogeneous group of >100 pulmonary disorders. ILDs are characterized by an irreversible architectural distortion and impaired gas exchange; however, there is great variability in the clinical course. ILD diagnosis requires a combination of clinical data, radiological imaging and histological findings (when a lung biopsy is required). At the same time, successful management of ILD patients strictly depends on an accurate and confident diagnosis. In this context, the detection of reliable biomarkers able to identify ILD subtypes, avoiding lung biopsy, as well as the capacity to stratify patients and predict over time the disease course, has become a primary aim for all research studies in this field.

  10. The relationships among birth season, sunlight exposure during infancy, and allergic disease

    PubMed Central

    Hwang, Jung Min; Oh, Se Hyun

    2016-01-01

    Purpose The recent increase in the prevalence of allergic diseases is hypothetically attributed to immune dysregulation in turn caused by a reduction in exposure to sunlight. We explored relationships between birth season, sunlight exposure, exercise duration, and an allergic disease. Methods We performed a questionnaire-based survey on allergic diseases among elementary school students. Birth time was categorized according to the season (summer and winter). Results The prevalence of atopic dermatitis (AD) "symptoms ever" was higher in the children born in winter than in those born in summer (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.03-1.49; P=0.024). Birth in winter was associated with an increase in the "symptoms in the past 12 months" prevalence of food allergy (FA) (aOR, 1.56; 95% CI, 1.09-2.24; P=0.015). The lifetime prevalence of allergic diseases except FA was higher in the children whose parents considered their sunlight exposure prior to 24 months of ageas inadequate than those who considered their exposure as adequate ("diagnosis ever" asthma: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; allergic rhinitis [AR]: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; AD: aOR, 1.26; 95% CI, 1.06-1.51; P=0.01). Neither recent sunlight exposure nor exercise duration was associated with the prevalence of an allergic disease. Conclusion Birth in winter may be associated with development of AD and FA. Inadequate sunlight exposure before the age of 24 months might possibly increase the risks of development of asthma, AR, and AD. PMID:27279886

  11. Lung disease in indigenous children.

    PubMed

    Chang, A B; Brown, N; Toombs, M; Marsh, R L; Redding, G J

    2014-12-01

    Children in indigenous populations have substantially higher respiratory morbidity than non-indigenous children. Indigenous children have more frequent respiratory infections that are, more severe and, associated with long-term sequelae. Post-infectious sequelae such as chronic suppurative lung disease and bronchiectasis are especially prevalent among indigenous groups and have lifelong impact on lung function. Also, although estimates of asthma prevalence among indigenous children are similar to non-indigenous groups the morbidity of asthma is higher in indigenous children. To reduce the morbidity of respiratory illness, best-practice medicine is essential in addition to improving socio-economic factors, (eg household crowding), tobacco smoke exposure, and access to health care and illness prevention programs that likely contribute to these issues. Although each indigenous group may have unique health beliefs and interfaces with modern health care, a culturally sensitive and community-based comprehensive care system of preventive and long term care can improve outcomes for all these conditions. This article focuses on common respiratory conditions encountered by indigenous children living in affluent countries where data is available.

  12. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  13. Neurotrophins in lung health and disease

    PubMed Central

    Prakash, YS; Thompson, Michael A; Meuchel, Lucas; Pabelick, Christina M; Mantilla, Carlos B; Zaidi, Syed; Martin, Richard J

    2010-01-01

    Neurotrophins (NTs) are a family of growth factors that are well-known in the nervous system. There is increasing recognition that NTs (nerve growth factor, brain-derived neurotrophic factor and NT3) and their receptors (high-affinity TrkA, TrkB and TrkC, and low-affinity p75NTR) are expressed in lung components including the nasal and bronchial epithelium, smooth muscle, nerves and immune cells. NT signaling may be important in normal lung development, developmental lung disease, allergy and inflammation (e.g., rhinitis, asthma), lung fibrosis and even lung cancer. In this review, we describe the current status of our understanding of NT signaling in the lung, with hopes of using aspects of the NT signaling pathway in the diagnosis and therapy of lung diseases. PMID:20524922

  14. Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

    SciTech Connect

    Maiellaro, Marília; Correa-Costa, Matheus; Vitoretti, Luana Beatriz; Gimenes Júnior, João Antônio; Câmara, Niels Olsen Saraiva; Tavares-de-Lima, Wothan; Farsky, Sandra Helena Poliselli; Lino-dos-Santos-Franco, Adriana

    2014-08-01

    Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment. - Highlights: • Formaldehyde exposure does not cause lung inflammation in pregnant rats. • Formaldehyde exposure suppresses allergic lung inflammation in the offspring. • Formaldehyde exposure induces oxidative stress in uterine environment.

  15. Use of antihistamines after serious allergic reaction to methimazole in pediatric Graves' disease.

    PubMed

    Toderian, Amy B; Lawson, Margaret L

    2014-05-01

    Antithyroid drugs are usually considered first-line therapy for management of pediatric Graves' disease because they avoid permanent hypothyroidism, provide a chance for remission, and are less invasive than the alternatives of thyroidectomy or radioactive iodine. Methimazole (MMI) is the only antithyroid drug recommended in pediatrics due to the risk of propylthiouracil-induced liver toxicity. Allergic reactions with MMI occur in up to 10% of patients and, when mild, can be managed with concurrent antihistamine therapy. Guidelines recommend discontinuation of MMI with serious allergic reactions. We present the case of an adolescent girl with Graves' disease and a serious allergic reaction after starting MMI whose family refused radioactive iodine and was reluctant to proceed to surgery. Antihistamine therapy was successfully used to allow continued treatment with MMI. This case demonstrates extension of management guidelines for minor cutaneous allergic reactions to MMI, through the use of antihistamines for a serious allergic reaction, allowing us to continue MMI and provide treatment consistent with the family's preferences and values.

  16. Allergic proctocolitis: the clinical evolution of a transitory disease with a familial trend. Case reports.

    PubMed

    Fagundes-Neto, Ulysses; Ganc, Arnaldo José

    2013-01-01

    Allergic colitis is a clinical manifestation of food allergy during the first months of life. It is estimated that genetic factors play a role in the expression of this allergic disease. This case report described the clinical progress of infants who were cousins from two distinct family groups with allergic colitis. Five infants under six months of age and of both sexes were studied, with a diagnosis of allergic colitis characterized clinically and histologically by (1) rectal bleeding; (2) exclusion of infectious causes of colitis; (3) disappearance of symptoms after elimination of cow's milk and dairy products from the child's and/or the mother's diet. Patients were submitted to the following diagnostic investigation: complete blood count; stool culture; parasitologic examination of stools; rectoscopy or colonoscopy; and rectal biopsy. Patient age varied from 40 days to six months; three were males. All patients presented with complaints of intense colic and rectal bleeding. The colonoscopy showed presence of hyperemia of the mucosa with microerosions and spontaneous bleeding upon the procedure. Microscopy revealed the existence of colitis with eosinophilia > 20 e/HPF. Patients were treated with a hypoallergenic formula and showed remission of symptoms. After one year of age, all were submitted to an oral challenge with a milk formula and presented food tolerance. Allergic colitis is a disease with evident genetic inheritance and a temporary character. PMID:23843067

  17. Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice

    PubMed Central

    2013-01-01

    Background With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. Methods We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. Results Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. Conclusions These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon

  18. [The lung in heart diseases].

    PubMed

    Sill, V

    1990-02-01

    The effects of "hypocirculation" and "hypercirculation" of the lungs are small. Hypocirculation has an influence of the ventilation/perfusion ratio, and can thus contribute to hypocapnia. In the early stages, hypercirculation--in particular via a left-to-right shung, leads to an increase in diffusion capacity; after a course of many years, a "counter-situation" occurs. Progressive pulmonary hypertension, as is exemplified for mitral stenosis, leads to measurable restrictive and obstructive impairment of function, and possible to unspecific hyper-reaction, as also, over the long-term, to a diminishement in membrane diffusion capacity. Chronic left heart failure is characterised by interstitial oedema at the level of the alveolar and bronchial capillary beds. The results are measurable restrictions in the static volumes, and in particular of the obstruction parameters and the closing volume that involve the small airways. In the individual case, no statement as to the extent of left heart failure is possible. In the passive pulmonary hypertension phase, diffusion capacity increases; in the further course of the disease, with development of interstitial and alveolar oedema, it decreases again. In acute left heart failure, the persistance and/or extent of pulmonary oedema is not determined solely by the magnitude of the pulmonary venous pressure. Permeability oedema--brought about by mediators--would appear to be significant on the basis of animal experiments. Not infrequently, left cardiac failure leads to small pleural effusions which occur in combination with substantial atelectasia, the aetiology of which is unclear. Interpretation difficulties are caused by the clinical findings and function-analytical data obtained in patients with a combination of chronic lung disease and reducted volume storage capacity of the pulmonary circulation and of the left heart failure, a common situation in the elderly patient. Diminished pulmonary function parameters that fail to

  19. Imaging of occupational and environmental lung diseases

    SciTech Connect

    Akira, M.

    2008-03-15

    The chest radiograph is the basic tool for identifying occupational and environmental lung diseases; however, its sensitivity and specificity for the diagnosis of occupational and environmental lung diseases are low. High-resolution CT is the optimal method of recognizing parenchymal abnormalities in occupational and environmental disease. With the exception of pleural plaques, the CT findings of occupational and environmental lung diseases are nonspecific. Therefore, correlation of imaging features with history of exposure, other clinical features, and sometimes pathology is needed for the diagnosis of pneumoconiosis.

  20. Cohabitation with a sick partner increases allergic lung inflammatory response in mice.

    PubMed

    Hamasato, Eduardo Kenji; de Lima, Ana Paula Nascimento; de Oliveira, Ana Paula Ligeiro; dos Santos Franco, Adriana Lino; de Lima, Wothan Tavares; Palermo-Neto, João

    2014-11-01

    results suggest that allergic lung inflammatory response exacerbation in CSP mice is a consequence of the psychological stress induced by forced cohabitation with the sick partner. Strong involvement of the sympathetic nervous system (SNS) through adrenaline and noradrenaline release and a shift of the Th1/Th2 cytokine profile toward a Th2 response were considered to be the mechanisms underlying the cell recruitment to the animal's airways.

  1. α-Tocopherol supplementation of allergic female mice inhibits development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates

    PubMed Central

    Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Soveg, Frank W.

    2014-01-01

    α-Tocopherol blocks responses to allergen challenge in allergic adult mice, but it is not known whether α-tocopherol regulates the development of allergic disease. Development of allergic disease often occurs early in life. In clinical studies and animal models, offspring of allergic mothers have increased responsiveness to allergen challenge. Therefore, we determined whether α-tocopherol blocked development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with α-tocopherol starting at mating. The pups from allergic mothers developed allergic lung responses, whereas pups from saline-treated mothers did not respond to the allergen challenge, and α-tocopherol supplementation of allergic female mice resulted in a dose-dependent reduction in eosinophils in the pup bronchoalveolar lavage and lungs after allergen challenge. There was also a reduction in pup lung CD11b+ dendritic cell subsets that are critical to development of allergic responses, but there was no change in several CD11b− dendritic cell subsets. Furthermore, maternal supplementation with α-tocopherol reduced the number of fetal liver CD11b+ dendritic cells in utero. In the pups, there was reduced allergen-induced lung mRNA expression of IL-4, IL-33, TSLP, CCL11, and CCL24. Cross-fostering pups at the time of birth demonstrated that α-tocopherol had a regulatory function in utero. In conclusion, maternal supplementation with α-tocopherol reduced fetal development of subsets of dendritic cells that are critical for allergic responses and reduced development of allergic responses in pups from allergic mothers. These results have implications for supplementation of allergic mothers with α-tocopherol. PMID:25015974

  2. FACTORS THAT INFLUENCE THE RELATIVE POTENCY OF DIESEL EXHAUST PARTICLES AS ADJUVANTS IN ALLERGIC AIRWAY DISEASE

    EPA Science Inventory

    Description: Studies have shown that diesel exhaust particles (DEP) worsen respiratory diseases including allergic asthma. The adjuvant effects of DEP in the airways have been widely reported; however, the precise determinants and mechanisms of these effects are ill-defined. S...

  3. Mechanisms of allergic disease - environmental and genetic determinants for the development of allergy.

    PubMed

    Campbell, D E; Boyle, R J; Thornton, C A; Prescott, S L

    2015-05-01

    Allergic disease can be viewed as an early manifestation of immune dysregulation. Environmental exposures including maternal inflammation, diet, nutrient balance, microbial colonization and toxin exposures can directly and indirectly influence immune programming in both pregnancy and the postnatal period. The intrauterine microclimate is critical for maternal and fetal immunological tolerance to sustain viable pregnancy, but appears susceptible to environmental conditions. Targeting aspects of the modern environment that promote aberrant patterns of immune response is logical for interventions aimed at primary prevention of allergic disease. Defining the mechanisms that underpin both natural and therapeutic acquisition of immunological tolerance in childhood will provide insights into the drivers of persistent immune dysregulation. In this review, we summarize evidence that allergy is a consequence of intrauterine and early life immune dysregulation, with specific focus on contributing environmental risk factors occurring preconception, in utero and in the early postnatal period. We explore the immunological mechanisms which underpin tolerance and persistence of allergic disease during childhood. It is likely that future investigations within these two domains will ultimately provide a road map for the primary prevention of allergic disease.

  4. Diffuse Cystic Lung Disease. Part II.

    PubMed

    Gupta, Nishant; Vassallo, Robert; Wikenheiser-Brokamp, Kathryn A; McCormack, Francis X

    2015-07-01

    The diffuse cystic lung diseases have a broad differential diagnosis. A wide variety of pathophysiological processes spanning the spectrum from airway obstruction to lung remodeling can lead to multifocal cyst development in the lung. Although lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis are perhaps more frequently seen in the clinic, disorders such as Birt-Hogg-Dubé syndrome, lymphocytic interstitial pneumonia, follicular bronchiolitis, and light-chain deposition disease are increasingly being recognized. Obtaining an accurate diagnosis can be challenging, and management approaches are highly disease dependent. Unique imaging features, genetic tests, serum studies, and clinical features provide invaluable clues that help clinicians distinguish among the various etiologies, but biopsy is often required for definitive diagnosis. In part II of this review, we present an overview of the diffuse cystic lung diseases caused by lymphoproliferative disorders, genetic mutations, or aberrant lung development and provide an approach to aid in their diagnosis and management.

  5. Inhaled Corticosteroids in Lung Diseases

    PubMed Central

    Raissy, Hengameh H.; Kelly, H. William; Harkins, Michelle

    2013-01-01

    Inhaled corticosteroids (ICSs) are used extensively in the treatment of asthma and chronic obstructive pulmonary disease (COPD) due to their broad antiinflammatory effects. They improve lung function, symptoms, and quality of life and reduce exacerbations in both conditions but do not alter the progression of disease. They decrease mortality in asthma but not COPD. The available ICSs vary in their therapeutic index and potency. Although ICSs are used in all age groups, younger and smaller children may be at a greater risk for adverse systemic effects because they can receive higher mg/kg doses of ICSs compared with older children. Most of the benefit from ICSs occurs in the low to medium dose range. Minimal additional improvement is seen with higher doses, although some patients may benefit from higher doses. Although ICSs are the preferred agents for managing persistent asthma in all ages, their benefit in COPD is more controversial. When used appropriately, ICSs have few adverse events at low to medium doses, but risk increases with high-dose ICSs. Although several new drugs are being developed and evaluated, it is unlikely that any of these new medications will replace ICSs as the preferred initial long-term controller therapy for asthma, but more effective initial controller therapy could be developed for COPD. PMID:23370915

  6. Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease.

    PubMed

    Yazdanbakhsh, M; van den Biggelaar, A; Maizels, R M

    2001-07-01

    The immune response to helminth infections has long been known to share key features with the allergic response. In particular, both are typified by enhanced T helper 2 (Th2) responses with high levels of interleukin-4 (IL-4), IL-5 and IL-13, accompanied by eosinophilia and abundant IgE production. Paradoxically, the geographical distribution of helminth parasitism and allergic disease is complementary rather than coincident. Thus, the question arises does the Th2 response to parasites protect or pre-empt the host from developing Th2-linked allergic manifestations? It is suggested that downregulatory immune mechanisms, which dampen the anti-parasite response, might benefit the host by blocking progression to atopic reactions. This is of relevance in explaining how the "hygiene hypothesis" might operate immunologically and in the design of therapeutics. PMID:11429321

  7. The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children

    PubMed Central

    Cairncross, Carolyn; Grant, Cameron; Stonehouse, Welma; Conlon, Cath; McDonald, Barry; Houghton, Lisa; Eyles, Darryl; Camargo, Carlos A.; Coad, Jane; von Hurst, Pamela

    2016-01-01

    Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child’s recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations ≥75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50–74.9 nmol/L (OR = 2.21, 1.33–3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children. PMID:27258306

  8. The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children.

    PubMed

    Cairncross, Carolyn; Grant, Cameron; Stonehouse, Welma; Conlon, Cath; McDonald, Barry; Houghton, Lisa; Eyles, Darryl; Camargo, Carlos A; Coad, Jane; von Hurst, Pamela

    2016-06-01

    Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child's recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations ≥75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50-74.9 nmol/L (OR = 2.21, 1.33-3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children.

  9. [An increase in allergic diseases in childhood--current hypotheses and possible prevention].

    PubMed

    Kurz, Herbert; Riedler, Jose

    2003-01-01

    During the last few decades there has ben a significant rise in the prevalence of allergic diseases such as asthma, hay fever and atopic dermatitis. Epidemiological studies strongly suggest that this increase is real and not due to changes in diagnostic labelling. It has become increasingly clear that a complex interplay between genetic and environmental factors account for this phenomenon. Genetically predisposed individuals are at an increased susceptibility to develop asthma or other allergic diseases when exposed to certain environmental or lifestyle factors. Particularly passive smoking has been shown to increase the risk for asthma in many studies and for atopy at least in some studies. This association is less clear for the exposure to sulfur dioxide, particulate matter, diesel exhaust and ozone. Lifestyle factors like socioeconomic status, sib-ship size, early childhood infections, dietary habits, growing up in antroposophic families or on a farm are more and more realised to be of great relevance for the development of allergic conditions. At the moment, there is a lot of uncertainty about which recommendations should be given for primary prevention. Recent studies have challenged the old paradigma that avoidance of early allergen contact could prevent the development of allergic disease. However, there is consensus that avoidance of smoking during pregnancy and avoidance of passive smoking during childhood should be recommended for primary prevention of asthma. PMID:12658963

  10. [An increase in allergic diseases in childhood--current hypotheses and possible prevention].

    PubMed

    Kurz, Herbert; Riedler, Jose

    2003-01-01

    During the last few decades there has ben a significant rise in the prevalence of allergic diseases such as asthma, hay fever and atopic dermatitis. Epidemiological studies strongly suggest that this increase is real and not due to changes in diagnostic labelling. It has become increasingly clear that a complex interplay between genetic and environmental factors account for this phenomenon. Genetically predisposed individuals are at an increased susceptibility to develop asthma or other allergic diseases when exposed to certain environmental or lifestyle factors. Particularly passive smoking has been shown to increase the risk for asthma in many studies and for atopy at least in some studies. This association is less clear for the exposure to sulfur dioxide, particulate matter, diesel exhaust and ozone. Lifestyle factors like socioeconomic status, sib-ship size, early childhood infections, dietary habits, growing up in antroposophic families or on a farm are more and more realised to be of great relevance for the development of allergic conditions. At the moment, there is a lot of uncertainty about which recommendations should be given for primary prevention. Recent studies have challenged the old paradigma that avoidance of early allergen contact could prevent the development of allergic disease. However, there is consensus that avoidance of smoking during pregnancy and avoidance of passive smoking during childhood should be recommended for primary prevention of asthma.

  11. General anesthesia exposure in early life reduces the risk of allergic diseases

    PubMed Central

    Kuo, Ho-Chang; Yang, Ya-Ling; Ho, Shu-Chen; Guo, Mindy Ming-Huey; Jiang, Jyun-Hong; Huang, Ying-Hsien

    2016-01-01

    Abstract General anesthesia (GA) has been used for second line treatment strategy for status asthmaticus in pediatric patients. The association between GA in children and risk of followed-up allergic diseases is unclear. This study aims to assess the risk of allergic diseases after GA in children. We did a nationwide retrospective cohort study by analyzing data from the National Health Insurance Research Database (NHIRD) in Taiwan. The subsequent risks for allergic diseases, including asthma (ICD-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between exposure to GA and none before 1 year of age throughout the follow-up period using the Cox proportional hazards model. Insurance claims data for 32,742 children younger than 1 year old from all insured children in the NHIRD. Of those, 2358 subjects were exposed to GA; 414 and 1944 children exposed to mask and intubation ventilation, respectively, served as the study cohort, whereas the remaining 30,384 children made up the comparison cohort. Children in the GA group were at a lower risk of developing asthma, AR and AD, with adjusted hazard ratios of 0.67 (0.62–0.72, 95%CI), 0.72 (0.68–0.77, 95%CI), 0.60 (0.56–0.64, 95%CI), respectively. Children who were exposed to GA in early life before 1 year of age had reduced risk of subsequently developing allergic diseases such as asthma, AD, and AR, when compared with general population. PMID:27428241

  12. [Respiratory physiotherapy in lung diseases].

    PubMed

    Opdekamp, C; Sergysels, R

    2003-09-01

    Functionally COPD is characterized by a reduction in airflow and an increase in dead space. Physical therapy and breathing training is designed to increase tidal volume, decrease respiratory rate and sense of dysponea. The respiratory exercises include controlled breathing, diaphragmatic and pursed-lip breathing. Postural drainage has, in most parts of the world, been replaced by airway clearance regimens that include forced expiratory manoeuvres or technique of breathing at different airflow and lung volume. Percussions and external or internal vibrations are seldom justified in adults. About instrumental chest physiotherapy with positive expiratory pressure support, the literature is confusing except for non invasive ventilation in acute stages. Dyspnoea, impaired exercise tolerance and reduced quality of life are common complaints in patients with chronic obstructive pulmonary disease. The efficacy of pulmonary rehabilitation has been strongly established by randomized controlled trials as reported by recent meta-analysis. The training intensity is of key importance. High-intensity training is feasible even in patients with more advanced COPD. There is substantial evidence that lower extremity endurance training should be included in the rehabilitation programs. There are beneficial effects of upper extremity endurance and strength training. Ventilatory muscle training may be considered in individual patients. Pulmonary rehabilitation programs must also be comprehensive and flexible to address each patients' need and include smoking cessation, optimal medical treatment, nutritional intervention, psychosocial support and health education. The maintenance of benefits after pulmonary rehabilitation is possible with minimal maintenance of activity. PMID:14606285

  13. The impact of pharmacogenetics in the treatment of allergic disease and asthma.

    PubMed

    Jones, Bridgette L

    2011-01-01

    Personalized medicine includes the application of genomic information in predicting disease and therapeutic response to ultimately individualize patient care. Pharmacogenetics is key in achieving true personalized care. However, the clinical applicability of genetic testing to "everyday medicine" is yet to be realized. This paper will discuss areas in allergic/inflammatory disease that have been impacted by pharmacogenetic research and how this application may be brought from the "bench to the bedside." PMID:22073496

  14. Home dampness, current allergic diseases, and respiratory infections among young adults

    PubMed Central

    Kilpelainen, M; Terho, E; Helenius, H; Koskenvuo, M

    2001-01-01

    BACKGROUND—The relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown.
METHODS—The association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18-25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated.
RESULTS—Visible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds ⩾4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21,95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity.
CONCLUSIONS—The risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.

 PMID:11359962

  15. An Allergic Lung Microenvironment Suppresses Carbon Nanotube-Induced Inflammasome Activation via STAT6-Dependent Inhibition of Caspase-1

    PubMed Central

    Shipkowski, Kelly A.; Taylor, Alexia J.; Thompson, Elizabeth A.; Glista-Baker, Ellen E.; Sayers, Brian C.; Messenger, Zachary J.; Bauer, Rebecca N.; Jaspers, Ilona; Bonner, James C.

    2015-01-01

    Background Multi-walled carbon nanotubes (MWCNTs) represent a human health risk as mice exposed by inhalation display pulmonary fibrosis. Production of IL-1β via inflammasome activation is a mechanism of MWCNT-induced acute inflammation and has been implicated in chronic fibrogenesis. Mice sensitized to allergens have elevated T-helper 2 (Th2) cytokines, IL-4 and IL-13, and are susceptible to MWCNT-induced airway fibrosis. We postulated that Th2 cytokines would modulate MWCNT-induced inflammasome activation and IL-1β release in vitro and in vivo during allergic inflammation. Methods THP-1 macrophages were primed with LPS, exposed to MWCNTs and/or IL-4 or IL-13 for 24 hours, and analyzed for indicators of inflammasome activation. C57BL6 mice were sensitized to house dust mite (HDM) allergen and MWCNTs were delivered to the lungs by oropharyngeal aspiration. Mice were euthanized 1 or 21 days post-MWCNT exposure and evaluated for lung inflammasome components and allergic inflammatory responses. Results Priming of THP-1 macrophages with LPS increased pro-IL-1β and subsequent exposure to MWCNTs induced IL-1β secretion. IL-4 or IL-13 decreased MWCNT-induced IL-1β secretion by THP-1 cells and reduced pro-caspase-1 but not pro-IL-1β. Treatment of THP-1 cells with STAT6 inhibitors, either Leflunomide or JAK I inhibitor, blocked suppression of caspase activity by IL-4 and IL-13. In vivo, MWCNTs alone caused neutrophilic infiltration into the lungs of mice 1 day post-exposure and increased IL-1β in bronchoalveolar lavage fluid (BALF) and pro-caspase-1 immuno-staining in macrophages and airway epithelium. HDM sensitization alone caused eosinophilic inflammation with increased IL-13. MWCNT exposure after HDM sensitization increased total cell numbers in BALF, but decreased numbers of neutrophils and IL-1β in BALF as well as reduced pro-caspase-1 in lung tissue. Despite reduced IL-1β mice exposed to MWCNTs after HDM developed more severe airway fibrosis by 21 days and

  16. Aeroparticles, Composition, and Lung Diseases

    PubMed Central

    Falcon-Rodriguez, Carlos I.; Osornio-Vargas, Alvaro R.; Sada-Ovalle, Isabel; Segura-Medina, Patricia

    2016-01-01

    Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood–air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-κB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like

  17. Aeroparticles, Composition, and Lung Diseases.

    PubMed

    Falcon-Rodriguez, Carlos I; Osornio-Vargas, Alvaro R; Sada-Ovalle, Isabel; Segura-Medina, Patricia

    2016-01-01

    Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood-air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-κB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like

  18. New developments providing mechanistic insight into the impact of the microbiota on allergic disease.

    PubMed

    McCoy, Kathy D; Köller, Yasmin

    2015-08-01

    The increase in allergic diseases over the past several decades is correlated with changes in the composition and diversity of the intestinal microbiota. Microbial-derived signals are critical for instructing the developing immune system and conversely, immune regulation can impact the microbiota. Perturbations in the microbiota composition may be especially important during early-life when the immune system is still developing, resulting in a critical window of opportunity for instructing the immune system. This review highlights recent studies investigating the role of the microbiome in susceptibility or development of allergic diseases with a focus on animal models that provide insight into the mechanisms and pathways involved. Identification of a causal link between reduced microbial diversity or altered microbial composition and increased susceptibility to immune-mediated diseases will hopefully pave the way for better preventive therapies.

  19. [Smoking-related interstitial lung diseases].

    PubMed

    Marten, Katharina

    2007-03-01

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

  20. [A birth cohort study on allergic diseases among toddlers in Northwest Germany].

    PubMed

    Pohlabeln, H; Jacobs, S; Böhmann, J

    2012-06-01

    In the late 1990s, a birth cohort study was conducted in the cities of Delmenhorst, Wilhelmshaven and Leer, where more than 3,000 newborn children were recruited in five hospitals. The baseline survey in the clinics was followed by three follow-up surveys 6, 12 and 24 months later. The prime concern of the study was to estimate prevalences and to conduct analyses concerning the association between breastfeeding as well as exposure to pets and the occurrence of allergy symptoms. Children living together with a dog in the same household were at higher risk of disease only if a familial predisposition of allergic diseases was present - without such a familial predisposition a dog in the same household seems to reduce the risk for atopic diseases during the first 2 years of life. A protective effect due to long breastfeeding could be observed in our study in particular in case of a paternal history of allergic diseases, whereas an exclusive maternal history of allergic diseases seems to increase the risk. The concept of the study has proved itself. Contacting mothers in obstetrical departments in hospitals as well as in medical offices of self-employed pediatricians has proven to be very practicable. With comparatively little effort a relatively large cohort was recruited, which allowed us to analyze longitudinal data, adequately taking into account several confounders as well as effect-modifying factors. PMID:22736168

  1. Preclinical lung disease in early rheumatoid arthritis.

    PubMed

    Robles-Perez, Alejandro; Luburich, Patricio; Rodriguez-Sanchon, Benigno; Dorca, Jordi; Nolla, Joan Miquel; Molina-Molina, Maria; Narvaez-Garcia, Javier

    2016-02-01

    Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels.

  2. Fas deficiency in mice with the Balb/c background induces blepharitis with allergic inflammation and hyper-IgE production in conjunction with severe autoimmune disease.

    PubMed

    Takahashi, Suzuka; Futatsugi-Yumikura, Shizue; Fukuoka, Ayumi; Yoshimoto, Tomohiro; Nakanishi, Kenji; Yonehara, Shin

    2013-05-01

    Fas (CD95) is a cell surface death receptor belonging to the tumor necrosis factor receptor superfamily, which mediates apoptosis-inducing signaling when activated by Fas ligand or its agonistic antibody. lpr mice with a loss of apoptosis-inducing function mutation in the Fas gene develop systemic autoimmune disease and lymphadenopathy but not allergic inflammation. In the case of Fas mutations including lpr and knockout (KO), background genes determine the incidence and severity of lymphadenopathy and histopathological manifestation of systemic autoimmunity: MRL-lpr/lpr mice and C57BL/6-lpr/lpr or C57BL/6 Fas KO mice develop severe and minimum disease, respectively. We generated Fas KO mice with the Balb/c background that show severer autoimmune phenotypes than MRL-lpr/lpr mice, such as critical infiltration of mononuclear cells into lung, liver and spleen, elevated serum levels of auto-antibodies and a decreased life span. To our astonishment, Balb/c Fas KO mice spontaneously develop blepharitis with not only autoimmune inflammation with deposition of auto-antibody but also allergic inflammation with infiltration by eosinophils and mast cells and show the capacity to strongly increase serum level of IgE and IgG1 along with their aging. Thus, Fas expression regulates development of not only autoimmune disease but also allergic inflammation.

  3. Italian Multicenter Cross-Sectional Study (AISAG) on light smoking and allergic diseases in adults.

    PubMed

    Lombardi, C; Passalacqua, G

    2016-03-01

    Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. On the basis of these contradictory data in the literature we have carried out a multicenter cross-sectional study to evaluate the relationship between some allergic conditions and exposure or not to active light smoking. The study was carried out between May 2013 and November 2013 in 22 different Italian hospitals. Patients with respiratory and/or food allergy, and aged 18 years and over, visited at Allergy Outpatient Clinics, were invited to participate. A total of 1586 allergic patients (21.6% smokers) with a mean age of 39.2 years (standard deviation, SD = 15.1) were included. We demonstrated that the prevalence of tobacco smoking was higher in patients with food allergy and in asthmatic patients in stage III-IV. But no other statistical differences were found at univariate analysis. The sensitization patterns of non-smokers and smokers were similar. Furthermore, tobacco smoking was associated with higher risk of food allergy and lower risk of asthma. Moreover, tobacco smoking was an independent risk factor for persistent respect to intermittent rhinitis, and for asthma GINA stage III-IV with respect to stage I-II.

  4. Time trends of the prevalence of asthma and allergic disease in Austrian children.

    PubMed

    Schernhammer, E S; Vutuc, C; Waldhör, T; Haidinger, G

    2008-03-01

    After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6-7 yr and 1516 children aged 12-14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6-7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12-14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors. PMID:18086231

  5. Mechanistic impact of outdoor air pollution on asthma and allergic diseases

    PubMed Central

    Zhang, Qingling; Qiu, Zhiming; Chung, Kian Fan

    2015-01-01

    Over the past decades, asthma and allergic diseases, such as allergic rhinitis and eczema, have become increasingly common, but the reason for this increased prevalence is still unclear. It has become apparent that genetic variation alone is not sufficient to account for the observed changes; rather, the changing environment, together with alterations in lifestyle and eating habits, are likely to have driven the increase in prevalence, and in some cases, severity of disease. This is particularly highlighted by recent awareness of, and concern about, the exposure to ubiquitous environmental pollutants, including chemicals with oxidant-generating capacities, and their impact on the human respiratory and immune systems. Indeed, several epidemiological studies have identified a variety of risk factors, including ambient pollutant gases and airborne particles, for the prevalence and the exacerbation of allergic diseases. However, the responsible pollutants remain unclear and the causal relationship has not been established. Recent studies of cellular and animal models have suggested several plausible mechanisms, with the most consistent observation being the direct effects of particle components on the generation of reactive oxygen species (ROS) and the resultant oxidative stress and inflammatory responses. This review attempts to highlight the experimental findings, with particular emphasis on several major mechanistic events initiated by exposure to particulate matters (PMs) in the exposure-disease relationship. PMID:25694815

  6. Role in Allergic Diseases of Immunological Cross-Reactivity between Allergens and Homologues of Parasite Proteins.

    PubMed

    Santiago, Helton da Costa; Nutman, Thomas B

    2016-01-01

    Implied under the rubric of the hygiene hypothesis is that helminth infection can protect against allergic disease. It is well known that helminths induce processes associated with type 2 immune responses, but they also induce important regulatory responses that can modulate these type 2-associated responses-modulation that influences responses to bystander antigens including allergens. Indeed, most epidemiological studies demonstrate a beneficial effect of helminth infection on atopy, but there are also convincing data to demonstrate that helminth infection can precipitate or worsen allergic inflammation/disease. Reasons for these disparate findings are much debated, but there is a school of thought that suggests that helminth-triggered type 2-associated responses, including IgE to cross-reactive aeroallergens, can offset the regulatory effects imposed by the same organisms. The cross-reactivity among helminths and allergenic tropomyosins dominated the antigen/allergen cross-reactivity field, but recent data suggest that cross-reactivity is much more common than previously appreciated. It has been demonstrated that a high degree of molecular similarity exists between allergens and helminth proteins. Thus, an understanding of the mechanisms underlying the response induced by helminth infection and their impact on the induction of allergic disease in the host are critical for designing therapies using iatrogenic infections or parasite products to treat inflammatory diseases and for developing vaccines against helminth parasites. PMID:27480900

  7. Interstitial Lung Disease in Idiopathic Inflammatory Myopathy

    PubMed Central

    Saketkoo, Lesley Ann; Ascherman, Dana P.; Cottin, Vincent; Christopher-Stine, Lisa; Danoff, Sonye K.; Oddis, Chester V.

    2011-01-01

    The lung is one of the most common extra-muscular targets in idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD) contributes to nearly 80% of the mortality in IIM with a reported prevalence of 65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical and laboratory findings of myositis, overt signs of muscle disease may be absent in the setting of significant lung disease. Understanding the varied scope of presentation of these diseases is essential to providing optimal patient care. This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention. PMID:21941374

  8. Respiratory Conditions Update: Restrictive Lung Disease.

    PubMed

    Robinson, H Coleman

    2016-09-01

    Restrictive lung diseases are a heterogeneous group of conditions characterized by a restrictive pattern on spirometry and confirmed by a reduction in total lung volume. Patients with more severe symptoms may have a reduced diffusing capacity of the lung for carbon monoxide. Etiologies can be intrinsic with lung parenchymal involvement, as in interstitial lung diseases, or extrinsic to the lung, as in obesity and neuromuscular disorders. Idiopathic pulmonary fibrosis is a chronic progressive interstitial pneumonia with fibrosis for which treatment is primarily supportive with oxygen therapy, pulmonary rehabilitation, and management of comorbid conditions. Newer drugs for idiopathic pulmonary fibrosis, such as pirfenidone and nintedanib, can slow disease progression. Referral for evaluation for lung transplantation is recommended for appropriate patients. Obstructive sleep apnea and obesity hypoventilation syndrome increasingly are common health issues, with symptoms that can include snoring, daytime somnolence, difficulty concentrating, fatigue, witnessed apneas, and morning headaches. Serum bicarbonate may serve as a biomarker in screening for subclinical obesity hypoventilation syndrome. Preoperative evaluations should assess pulmonary risk in addition to cardiac risk with a thorough history, laboratory tests, and functional capacity assessments. Optimization of management may include weight loss, pulmonary rehabilitation, oxygen therapy, and respiratory support. PMID:27576233

  9. Histopathologic approach to the surgical lung biopsy in interstitial lung disease.

    PubMed

    Jones, Kirk D; Urisman, Anatoly

    2012-03-01

    Interpretation of lung biopsy specimens is an integral part in the diagnosis of interstitial lung disease (ILD). The process of evaluating a surgical lung biopsy for disease involves answering several questions. Unlike much of surgical pathology of neoplastic lung disease, arriving at the correct diagnosis in nonneoplastic lung disease often requires correlation with clinical and radiologic findings. The topic of ILD or diffuse infiltrative lung disease covers several hundred entities. This article is meant to be a launching point in the clinician's approach to the histologic evaluation of lung disease.

  10. Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol.

    PubMed Central

    Church, M. K.; Hiroi, J.

    1987-01-01

    The ability of the anti-allergic drugs, sodium cromoglycate (SCG), lodoxamide, traxanox, RU31156 and the beta-adrenoceptor agonist salbutamol to inhibit IgE-dependent histamine and prostaglandin D2 (PGD2) release was assessed using human dispersed lung mast cells. The anti-allergic drugs were weak inhibitors of histamine release, high concentrations (100-1000 microM) producing less than 35% inhibition. Salbutamol produced 39% inhibition at 10 microM. The efficacy of both SCG and salbutamol was inversely related to the concentration of anti-IgE used for challenge and to the degree of histamine release. Rapid tachyphylaxis was observed with all anti-allergic drugs but not with salbutamol. Cross-tachyphylaxis was observed between SCG and the other anti-allergic drugs, suggesting a common mechanism of action. No cross-tachyphylaxis was observed between SCG and salbutamol. SCG was significantly (P less than 0.001) more effective in inhibiting PGD2 than it was histamine release. Preferential inhibition of PGD2 compared with histamine release was less marked (P less than 0.05) with salbutamol and not significant with the other anti-allergic drugs. Mast cells dispersed by enzymatic digestion of human lung released more histamine on immunological challenge than mechanically dispersed cells obtained by fine chopping of tissue. Enzyme treatment of mechanically dispersed cells removed this difference. Enzymatically and mechanically dispersed cells responded similarly to the inhibitory effects of SCG and salbutamol. Our results suggest that salbutamol is a more effective inhibitor of mediator release from human lung mast cells than anti-allergic drugs. However, with the low levels of mediator release achieved during an allergic reaction in man in vivo, both salbutamol and SCG are likely to be effective inhibitors of both preformed and newly generated mediators. PMID:2435353

  11. EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS

    EPA Science Inventory

    EFFECTS OF ALLERGIC AIRWAYS DISEASE ON INFLUENZA VIRUS INFECTION IN BROWN NORWAY RATS (P. Singhl, D.W. Winsett2, M.J. Daniels2,
    C.A.J. Dick', K.B. Adlerl and M.I. Gilmour2, INCSU, Raleigh, N.C., 2NHEERL/ORD/ USEPA, RTP, N.C. and 3UNC, Chapel Hill, N.C.)The interaction between ...

  12. Grass pollen allergens globally: the contribution of subtropical grasses to burden of allergic respiratory diseases.

    PubMed

    Davies, J M

    2014-06-01

    types of subtropical grass pollens to achieve optimal diagnosis and treatment of patients with allergic respiratory disease in subtropical regions of the world.

  13. Interstitial lung disease in systemic sclerosis.

    PubMed

    Wells, Athol U

    2014-10-01

    Based on international collaborative data, interstitial lung disease is now the most frequent cause of death in systemic sclerosis (SSc), having supplanted renal crisis in that regard. Despite detailed explorations of candidate mediators, no primary pathway in the pathogenesis of interstitial lung disease associated with SSc (SSc-ILD) has been definitively identified and, therefore, treatment with current agents is only partially successful. However, as immunomodulatory agents do, on average, retard progression of lung disease, early identification of SSc-ILD, using thoracic high resolution computed tomography (HRCT), is highly desirable. The decision whether to introduce therapy immediately is often difficult as the balance of risk and benefit favours a strategy of careful observation when lung disease is very limited, especially in long-standing SSc. The threshold for initiating treatment is substantially reduced when lung disease is severe, systemic disease is short in duration or ongoing progression is evident, based on pulmonary function tests and symptoms. This review summarises epidemiology, pathogenesis, difficult clinical problems and management issues in SSc-ILD.

  14. [Modern Views on Children's Interstitial Lung Disease].

    PubMed

    Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

    2015-01-01

    Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

  15. [Modern Views on Children's Interstitial Lung Disease].

    PubMed

    Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

    2015-01-01

    Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article. PMID:26234096

  16. Location, Location, Location: Localized Memory Cells Take Residence in the Allergic Lung.

    PubMed

    Lloyd, Clare M; Harker, James A

    2016-01-19

    Understanding the localization of cells is important as local environmental cues influence both phenotype and effector function. In this issue of Immunity, Pepper and colleagues find that allergen-specific tissue-resident memory T cells are maintained by IL-2 and are key drivers of allergic pathology.

  17. Location, Location, Location: Localized Memory Cells Take Residence in the Allergic Lung.

    PubMed

    Lloyd, Clare M; Harker, James A

    2016-01-19

    Understanding the localization of cells is important as local environmental cues influence both phenotype and effector function. In this issue of Immunity, Pepper and colleagues find that allergen-specific tissue-resident memory T cells are maintained by IL-2 and are key drivers of allergic pathology. PMID:26789918

  18. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis

    PubMed Central

    Ierodiakonou, Despo; Khan, Tasnia; Chivinge, Jennifer; Robinson, Zoe; Geoghegan, Natalie; Jarrold, Katharine; Afxentiou, Thalia; Reeves, Tim; Cunha, Sergio; Trivella, Marialena; Garcia-Larsen, Vanessa; Leonardi-Bee, Jo

    2016-01-01

    Objective To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. Design Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. Data sources Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. Eligibility criteria for selecting studies Prospective intervention trials of hydrolysed cows’ milk formula compared with another hydrolysed formula, human breast milk, or a standard cows’ milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. Results 37 eligible intervention trials of hydrolysed formula were identified, including over 19 000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows’ milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I2=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I2=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I2=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could prevent allergy to cows’ milk. Conclusion These findings do not support current guidelines

  19. Common lung conditions: environmental pollutants and lung disease.

    PubMed

    Delzell, John E

    2013-06-01

    Exposure to environmental pollutants can have short- and long-term effects on lung health. Sources of air pollution include gases (eg, carbon monoxide, ozone) and particulate matter (eg, soot, dust). In the United States, the Environmental Protection Agency regulates air pollution. Elevated ozone concentrations are associated with increases in lung-related hospitalizations and mortality. Elevated particulate matter pollution increases the risk of cardiopulmonary and lung cancer mortality. Occupations with high exposures to pollutants (eg, heavy construction work, truck driving, auto mechanics) pose higher risk of chronic obstructive lung disease. Some industrial settings (eg, agriculture, sawmills, meat packing plants) also are associated with higher risks from pollutants. The Environmental Protection Agency issues an air quality index for cities and regions in the United States. The upper levels on the index are associated with increases in asthma-related emergency department visits and hospitalizations. Damp and moldy housing might make asthma symptoms worse; individuals from lower socioeconomic groups who live in lower quality housing are particularly at risk. Other household exposures that can have negative effects on lung health include radon, nanoparticles, and biomass fuels. PMID:23767420

  20. NADPH Oxidases in Lung Health and Disease

    PubMed Central

    Bernard, Karen; Hecker, Louise; Luckhardt, Tracy R.; Cheng, Guangjie

    2014-01-01

    Abstract Significance: The evolution of the lungs and circulatory systems in vertebrates ensured the availability of molecular oxygen (O2; dioxygen) for aerobic cellular metabolism of internal organs in large animals. O2 serves as the physiologic terminal acceptor of mitochondrial electron transfer and of the NADPH oxidase (Nox) family of oxidoreductases to generate primarily water and reactive oxygen species (ROS), respectively. Recent advances: The purposeful generation of ROS by Nox family enzymes suggests important roles in normal physiology and adaptation, most notably in host defense against invading pathogens and in cellular signaling. Critical issues: However, there is emerging evidence that, in the context of chronic stress and/or aging, Nox enzymes contribute to the pathogenesis of a number of lung diseases. Future Directions: Here, we review evolving functions of Nox enzymes in normal lung physiology and emerging pathophysiologic roles in lung disease. Antioxid. Redox Signal. 20, 2838–2853. PMID:24093231

  1. The Bacterial Microbiota in Inflammatory Lung Diseases

    PubMed Central

    Huffnagle, Gary B.; Dickson, Robert P.

    2016-01-01

    Numerous lines of evidence, ranging from recent studies back to those in the 1920's, have demonstrated that the lungs are NOT bacteria-free during health. We have recently proposed that the entire respiratory tract should be considered a single ecosystem extending from the nasal and oral cavities to the alveoli, which includes gradients and niches that modulate microbiome dispersion, retention, survival and proliferation. Bacterial exposure and colonization of the lungs during health is most likely constant and transient, respectively. Host microanatomy, cell biology and innate defenses are altered during chronic lung disease, which in turn, alters the dynamics of bacterial turnover in the lungs and can lead to longer term bacterial colonization, as well as blooms of well-recognized respiratory bacterial pathogens. A few new respiratory colonizers have been identified by culture-independent methods, such as Pseudomonas fluorescens; however, the role of these bacteria in respiratory disease remains to be determined. PMID:26122174

  2. Nutrition in early life and the risk of asthma and allergic disease.

    PubMed

    Wyness, Laura

    2014-07-01

    The prevalence of reported cases of asthma and allergic disease has seen a marked increase throughout the world since the 1960s, particularly in more developed, westernised countries. A key focus of research in this area has been the possible adverse effects of foetal and infant exposure to food allergens. There is some evidence that foetal and infant exposure to a range of allergens via the mother and her breast milk is important in the development of normal immune tolerance. Current advice is that pregnant and breastfeeding women do not need to avoid potential food allergens unless they are allergic themselves, or are advised to modify their diet by a health professional. Delaying the introduction of common food allergies beyond 6 months is unlikely to reduce the likelihood of food allergy and allergic disease. The findings of current ongoing trials investigating the potential benefits of early introduction on allergenic foods into the diet of children-as well as the comprehensive review of complementary and young-child feeding advice currently being conducted by the Scientific Advisory Committee on Nutrition-will help inform guidance in this area.

  3. Probiotics as Additives on Therapy in Allergic Airway Diseases: A Systematic Review of Benefits and Risks

    PubMed Central

    Das, Rashmi Ranjan; Naik, Sushree Samiksha; Singh, Meenu

    2013-01-01

    Background. We conducted a systematic review to find out the role of probiotics in treatment of allergic airway diseases.  Methods. A comprehensive search of the major electronic databases was done till March 2013. Trials comparing the effect of probiotics versus placebo were included. A predefined set of outcome measures were assessed. Continuous data were expressed as standardized mean difference with 95% CI. Dichotomous data were expressed as odds ratio with 95% CI. P value < 0.05 was considered as significant. Results. A total of 12 studies were included. Probiotic intake was associated with a significantly improved quality of life score in patients with allergic rhinitis (SMD −1.9 (95% CI −3.62, −0.19); P = 0.03), though there was a high degree of heterogeneity. No improvement in quality of life score was noted in asthmatics. Probiotic intake also improved the following parameters: longer time free from episodes of asthma and rhinitis and decrease in the number of episodes of rhinitis per year. Adverse events were not significant. Conclusion. As the current evidence was generated from few trials with high degree of heterogeneity, routine use of probiotics as an additive on therapy in subjects with allergic airway diseases cannot be recommended. PMID:23956972

  4. Association Between Vitamin D Deficiency and Allergic Diseases

    PubMed Central

    Malinowski, Bartosz; Bergmann, Katarzyna

    2011-01-01

    Vitamin D is important for the regulation of bone and muscle metabolism and other functions in the human body. The hydroxylated forms of vitamin D2 and D3 are the most important, however only 1,25(OH)D2 is a fully active product. This hormone exert its pleiotropic actions via the specific receptor VDR, an important transcription factor. The optimal vitamin D concentration in the blood is >20 ng/mL whereas insufficiency and deficiency are 10-20 ng/mL and <10 ng/mL, respectively. To maintain the optimal vitamin D status the total vitamin D intake in children should be at least 400 IU/day. Several studies have shown the effects of vitamin D on proinflammatory cytokines, regulatory T cells and immune response. Vitamin D is a very important activator of the immune response, and in hypovitaminosis D, T killer cells are not able to fight off serious infections. A negative correlation between IgE and vitamin D concentration and a positive relation between vitamin D and lung function was documented in children and teenagers with asthma. In asthmatic children the vitamin D deficiency is associated with a higher corticosteroid use. Vitamin D supplementation in patients with steroid resistant asthma can potentially increase the glucocorticoid therapeutic response. Recently, a new mediator in allergy pathogenesis was reported - IL-33 and its soluble receptor ST2. IL-33 promotes the Th2 lymphocytes response as well as the activation of both mast cells and eosinophils via the ST2 receptor. “A vitamin is a substance that makes you ill if you don’t eat it.” (Albert Szent-Gyorgyi, Nobel Prize winner in Physiology and Medicine, 1937)

  5. Association Between Vitamin D Deficiency and Allergic Diseases

    PubMed Central

    Malinowski, Bartosz; Bergmann, Katarzyna

    2011-01-01

    Vitamin D is important for the regulation of bone and muscle metabolism and other functions in the human body. The hydroxylated forms of vitamin D2 and D3 are the most important, however only 1,25(OH)D2 is a fully active product. This hormone exert its pleiotropic actions via the specific receptor VDR, an important transcription factor. The optimal vitamin D concentration in the blood is >20 ng/mL whereas insufficiency and deficiency are 10-20 ng/mL and <10 ng/mL, respectively. To maintain the optimal vitamin D status the total vitamin D intake in children should be at least 400 IU/day. Several studies have shown the effects of vitamin D on proinflammatory cytokines, regulatory T cells and immune response. Vitamin D is a very important activator of the immune response, and in hypovitaminosis D, T killer cells are not able to fight off serious infections. A negative correlation between IgE and vitamin D concentration and a positive relation between vitamin D and lung function was documented in children and teenagers with asthma. In asthmatic children the vitamin D deficiency is associated with a higher corticosteroid use. Vitamin D supplementation in patients with steroid resistant asthma can potentially increase the glucocorticoid therapeutic response. Recently, a new mediator in allergy pathogenesis was reported - IL-33 and its soluble receptor ST2. IL-33 promotes the Th2 lymphocytes response as well as the activation of both mast cells and eosinophils via the ST2 receptor. “A vitamin is a substance that makes you ill if you don’t eat it.” (Albert Szent-Gyorgyi, Nobel Prize winner in Physiology and Medicine, 1937) PMID:27683389

  6. Treatment of Lung Carcinoid by Type and Extent of Disease

    MedlinePlus

    ... your doctor about lung carcinoid tumors? Treatment of lung carcinoid, by type and extent of disease The ... those that can’t be removed completely Resectable lung carcinoid tumors Resectable carcinoid tumors haven’t spread ...

  7. How Are Asbestos-Related Lung Diseases Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Are Asbestos-Related Lung Diseases Treated? No treatments can reverse the effects ... then draw out the excess fluid. Treatments for Lung Cancer and Mesothelioma If you have lung cancer ...

  8. COMPARISON OF LUNG ATTENUATION AND HETEROGENEITY BETWEEN CATS WITH EXPERIMENTALLY INDUCED ALLERGIC ASTHMA, NATURALLY OCCURRING ASTHMA AND NORMAL CATS.

    PubMed

    Masseau, Isabelle; Banuelos, Alina; Dodam, John; Cohn, Leah A; Reinero, Carol

    2015-01-01

    Airway remodeling is a prominent feature of feline allergic asthma but requires biopsy for characterization. Computed tomography (CT) has appeal as a minimally invasive diagnostic test. The purpose of this prospective case-control study was to compare indices of airway remodeling between cats with experimentally induced, spontaneous asthma and healthy unaffected cats using CT. We hypothesized that experimental and spontaneous feline asthma would have similar CT airway remodeling characteristics and that these would be significantly different in healthy cats. Experimentally induced asthmatic research cats (n = 5), spontaneously asthmatic pet cats (n = 6), and healthy research cats (n = 5) were scanned unrestrained using a 64-detector row CT scanner. Inspiratory breath-hold CT scans were also performed in experimentally induced asthmatic and healthy cats. Mean ± extent variation of lung attenuation for each cat was determined using an airway inspector software program and CT images were scored for lung heterogeneity by a board-certified veterinary radiologist who was unaware of cat group status. Groups were compared using one-way ANOVA (unrestrained scans) and the Student's t-test (anesthetized scans) with significance defined as P < 0.10. Experimentally asthmatic and spontaneously asthmatic cats had significantly (P = 0.028 and P = 0.073, respectively) increased lung attenuation compared to healthy cats. Heterogeneity scores were higher in experimentally induced asthmatic cat than in healthy cats. Objective quantification of lung heterogeneity and lung volume did not differ among the three groups (P = 0.311, P = 0.181, respectively). Findings supported our hypothesis. Inspiratory breath-hold anesthetized CT scans facilitated discrimination between asthmatic and healthy cats in comparison to unrestrained CT scans.

  9. Allergic- and immune-associated diseases of the urinary tract.

    PubMed

    Nichols, R

    1994-07-01

    Glomerular injury has a decided immunologic basis. Any infectious, inflammatory, neoplastic, or degenerative processes capable of sustained antigenic stimulation can induce immune-mediated glomerular injury. A variety of conditions and antigens, both endogenous and exogenous, are known to initiate immunologic glomerular damage. In many clinical situations, however, the precise antigenic source is occult and unrecognizable, and the glomerular disease is referred to as idiopathic. PMID:7975046

  10. The effect of hypoallergenic formula on the occurrence of allergic diseases in high risk infants.

    PubMed

    Tsai, Y T; Chou, C C; Hsieh, K H

    1991-01-01

    To study the influence of hypoallergenic milk on the occurrence of allergic diseases, thirty-three high risk, normal full-term newborns were divided into two groups with comparable family allergy score (FAS) and cord serum IgE. Group A consisted of 18 babies fed since birth with regular formula, while group B included 15 babies fed breast milk and/or NAN H.A. (Hypoallergenic infant formula) for the first 6 months of life. Close clinical observations for the appearance of atopic dermatitis, allergic rhinitis and wheezing as well as serial examination of total serum IgE and milk-specific IgE antibodies were done during the first year of life. The results showed: 1) Infants fed regular formula had a higher incidence of moderate to severe atopic dermatitis (AD) and allergic rhinitis (AR) than those fed NAN H.A. (39% vs 13% for AD; and 33% vs 13% for AR), but the difference was not significant. There was no difference in the incidence of wheezing between these two groups; 2) There was no relationship between cord blood IgE and FAS; 3) Neither the cord blood IgE nor FAS influenced the occurrence of allergic diseases and total serum IgE at one year of age; 4) Hypoallergenic milk (NAN H.A.) could support normal growth and development. In conclusion, a higher incidence of moderate to severe AD and AR was found in high risk infants fed regular formula than in those fed hypoallergenic milk. However, a study with a larger number of babies and a longer period of follow-up is needed to obtain a solid conclusion.

  11. Exposure to ambient bioaerosols is associated with allergic skin diseases in Greater Taipei residents.

    PubMed

    Kallawicha, Kraiwuth; Chuang, Ying-Chih; Lung, Shih-Chun Candice; Han, Bor-Cheng; Ting, Yi-Fang; Chao, Hsing Jasmine

    2016-09-01

    Allergic skin diseases may result from various types of chemical and biological allergens. This study investigated the association between ambient bioaerosol exposure and allergic skin diseases by using the exposure data obtained from land use regression models and interpolated data. Data on daily average outpatient visits for atopic dermatitis (ICD-9-CM 691.8) and contact dermatitis and other eczema (ICD-9-CM 692.9) between November 2011 and August 2012 were obtained from the National Health Insurance Research Database. A generalized estimating equation was used to analyze the associations between the skin diseases and ambient bioaerosol levels. The results indicated that during the study period, contact dermatitis and other eczema were more prevalent than atopic dermatitis in the study area. Most cases were observed in districts of Taipei City and 3 major districts of New Taipei City, namely Xinzhuang, Banqiao, and Xindian. In univariate analysis, most bioaerosols were positively associated with both skin diseases. After adjustment for air pollution and sociodemographic factors, exposure to total fungal spores was significantly associated with atopic dermatitis in males (relative risk [RR] = 1.12; 95% confidence interval [CI] = 1.05-1.19). Contact dermatitis and other eczema had significant relationships with Cladosporium in males (RR = 1.07; 95% CI = 1.02-1.14) and with Aspergillus/Penicillium in females (RR = 1.04; 95% CI = 1.02-1.07). Meteorological parameters, namely wind speed, temperature, and rainfall, were also significantly associated with skin diseases. Our findings reveal that exposure to ambient bioaerosols is a significant and independent risk factor for allergic skin diseases. PMID:27389548

  12. Rheumatoid arthritis-associated interstitial lung disease

    PubMed Central

    Solomon, Joshua J; Brown, Kevin K

    2012-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting 1% of the US population. Patients can have extra-articular manifestations of their disease and the lungs are commonly involved. RA can affect any compartment of the respiratory system and high resolution computed tomography (HRCT) of the lung is abnormal in over half of these patients. Interstitial lung disease is a dreaded complication of RA. It is more prevalent in smokers, males, and those with high antibody titers. The pathogenesis is unknown but data suggest an environmental insult in the setting of a genetic predisposition. Smoking may play a role in the pathogenesis of disease through citrullination of protein in the lung leading to the development of autoimmunity. Patients usually present in middle age with cough and dyspnea. Pulmonary function testing most commonly shows reduced diffusion capacity for carbon monoxide and HRCT reveals a combination of reticulation and ground glass abnormalities. The most common pattern on HRCT and histopathology is usual interstitial pneumonia (UIP), with nonspecific interstitial pneumonia seen less frequently. There are no large-scale well-controlled treatment trials. In severe or progressive cases, treatment usually consists of corticosteroids with or without a cytotoxic agent for 6 months or longer. RA interstitial lung disease is progressive; over half of patients show radiographic progression within 2 years. Patients with a UIP pattern on biopsy have a survival similar to idiopathic pulmonary fibrosis.

  13. The effect of parental allergy on childhood allergic diseases depends on the sex of the child

    PubMed Central

    Arshad, S. Hasan; Karmaus, Wilfried; Raza, Abid; Kurukulaaratchy, Ramesh J.; Matthews, Sharon M.; Holloway, John W; Sadeghnejad, Alireza; Zhang, Hongmei; Roberts, Graham; Ewart, Susan L.

    2012-01-01

    Background Parent of origin effect is important in understanding the genetic basis of childhood allergic diseases and to improve our ability to identify high risk children. Objective To investigate parent of origin effect in childhood allergic diseases. Methods The Isle of Wight Birth Cohort (n=1,456) has been examined at 1, 2, 4, 10 and 18-years. Information on prevalence of asthma, eczema, rhinitis and environmental factors was obtained using validated questionnaires. Skin prick tests were carried out at ages 4, 10 and 18 year, and total IgE at 10 and 18 years. Parental history of allergic disease was assessed soon after the birth of the child when maternal IgE was also measured. Prevalence ratios (PR) and their 95% confidence intervals (CI) were estimated, applying log-linear models, adjusted for confounding variables. Results When stratified for sex of the child, maternal asthma was associated with asthma in girls [PR:1.91 (CI:1.34–2.72), p=0.0003], but not in boys [PR:1.29 (CI:0.85–1.96), p=0.23), while paternal asthma was associated with asthma in boys [PR:1.99 (CI:1.42–2.79), p<0.0001], but not in girls [PR: 1.03 (0.59–1.80) p=0.92). Maternal eczema increased the risk of eczema in girls [PR: 1.92 (CI: 1.37–2.68); p=0.0001] only, while paternal eczema did the same for boys (PR: 2.07 (CI:1.32–3.25); P=0.002). Similar trends were observed when the effect of maternal and paternal allergic disease was assessed for childhood atopy and when maternal total IgE was related to total IgE in children at age 10 and 18 years. Conclusions The current study indicates a sex dependent association of parental allergic conditions with childhood allergies; maternal allergy increasing the risk in girls and paternal allergy in boys. This has implications for childhood allergy prediction and prevention. PMID:22607991

  14. Toward precision medicine and health: Opportunities and challenges in allergic diseases.

    PubMed

    Galli, Stephen Joseph

    2016-05-01

    Precision medicine (also called personalized, stratified, or P4 medicine) can be defined as the tailoring of preventive measures and medical treatments to the characteristics of each patient to obtain the best clinical outcome for each person while ideally also enhancing the cost-effectiveness of such interventions for patients and society. Clearly, the best clinical outcome for allergic diseases is not to get them in the first place. To emphasize the importance of disease prevention, a critical component of precision medicine can be referred to as precision health, which is defined herein as the use of all available information pertaining to specific subjects (including family history, individual genetic and other biometric information, and exposures to risk factors for developing or exacerbating disease), as well as features of their environments, to sustain and enhance health and prevent the development of disease. In this article I will provide a personal perspective on how the precision health-precision medicine approach can be applied to the related goals of preventing the development of allergic disorders and providing the most effective diagnosis, disease monitoring, and care for those with these prevalent diseases. I will also mention some of the existing and potential challenges to achieving these ambitious goals. PMID:27155026

  15. Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring.

    PubMed

    Maiellaro, Marília; Correa-Costa, Matheus; Vitoretti, Luana Beatriz; Gimenes Júnior, João Antônio; Câmara, Niels Olsen Saraiva; Tavares-de-Lima, Wothan; Farsky, Sandra Helena Poliselli; Lino-dos-Santos-Franco, Adriana

    2014-08-01

    Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment.

  16. Epigenetic contributions to the developmental origins of adult lung disease.

    PubMed

    Joss-Moore, Lisa A; Lane, Robert H; Albertine, Kurt H

    2015-04-01

    Perinatal insults, including intrauterine growth restriction, preterm birth, maternal exposure to toxins, or dietary deficiencies produce deviations in the epigenome of lung cells. Occurrence of perinatal insults often coincides with the final stages of lung development. The result of epigenome disruptions in response to perinatal insults during lung development may be long-term structural and functional impairment of the lung and development of lung disease. Understanding the contribution of epigenetic mechanisms to life-long lung disease following perinatal insults is the focus of the developmental origins of adult lung disease field. DNA methylation, histone modifications, and microRNA changes are all observed in various forms of lung disease. However, the perinatal contribution to such epigenetic mechanisms is poorly understood. Here we discuss the developmental origins of adult lung disease, the interplay between perinatal events, lung development and disease, and the role that epigenetic mechanisms play in connecting these events.

  17. Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

    PubMed

    Tanno, L K; Calderon, M A; Goldberg, B J; Gayraud, J; Bircher, A J; Casale, T; Li, J; Sanchez-Borges, M; Rosenwasser, L J; Pawankar, R; Papadopoulos, N G; Demoly, P

    2015-06-01

    The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11.

  18. Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

    PubMed

    Tanno, L K; Calderon, M A; Goldberg, B J; Gayraud, J; Bircher, A J; Casale, T; Li, J; Sanchez-Borges, M; Rosenwasser, L J; Pawankar, R; Papadopoulos, N G; Demoly, P

    2015-06-01

    The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11. PMID:25736171

  19. Diffuse Cystic Lung Diseases: Diagnostic Considerations.

    PubMed

    Xu, Kai-Feng; Feng, Ruie; Cui, Han; Tian, Xinlun; Wang, Hanping; Zhao, Jing; Huang, Hui; Zhang, Weihong; Lo, Bee Hong

    2016-06-01

    Diffuse cystic lung disease (DCLD) is a group of heterogeneous diseases that present as diffuse cystic changes in the lung on computed tomography of the chest. Most DCLD diseases are rare, although they might resemble common diseases such as emphysema and bronchiectasis. Main causes of DCLD include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, pulmonary Langerhans cell histiocytosis, lymphoid interstitial pneumonia, amyloidosis, light-chain deposition disease, Sjögren syndrome, and primary or metastatic neoplasm. We discuss clinical factors that are helpful in the differential diagnosis of DCLDsuch as sex and age, symptoms and signs, extrapulmonary presentations, cigarette smoking, and family history. Investigations for DCLD include high-resolution computed tomography, biochemical and histopathological studies, genetic tests, pulmonary function tests, and bronchoscopic and video-assisted thoracoscopic biopsies. A proposed diagnostic algorithm would enhance ease of diagnosing most cases of DCLD. PMID:27231867

  20. Biomarkers in Paediatric Cystic Fibrosis Lung Disease.

    PubMed

    Ramsey, Kathryn A; Schultz, André; Stick, Stephen M

    2015-09-01

    Biomarkers in cystic fibrosis are used i. for the measurement of cystic fibrosis transmembrane regulator function in order to diagnose cystic fibrosis, and ii. to assess aspects of lung disease severity (e.g. inflammation, infection). Effective biomarkers can aid disease monitoring and contribute to the development of new therapies. The tests of cystic fibrosis transmembrane regulator function each have unique strengths and weaknesses, and biomarkers of inflammation, infection and tissue destruction have the potential to enhance the management of cystic fibrosis through the early detection of disease processes. The development of biomarkers of cystic fibrosis lung disease, in particular airway inflammation and infection, is influenced by the challenges of obtaining relevant samples from infants and children for whom early detection and treatment of disease might have the greatest long term benefits.

  1. The lung in sickle cell disease.

    PubMed

    Knight, J; Murphy, T M; Browning, I

    1999-09-01

    Sickle cell disease is the most common inherited disorder in African-Americans. Although the primary defect is hematological, the changes in the erythrocytes lead to a vasculopathy with multiorgan injury. The pulmonary complications, i.e., acute chest syndrome and chronic sickle cell lung disease, are significant causes of morbidity and mortality. The pulmonary manifestations result from a unique constellation of factors which come into play in sickle cell disease. Based on the growing understanding of the molecular and cellular biology of sickle cell disease, new therapies are being developed that are likely to ameliorate the natural history of this disease and its complications. PMID:10495338

  2. [Interstitial lung diseases. The pattern is important].

    PubMed

    Fink, L

    2014-11-01

    Interstitial lung diseases (ILDs) comprise a number of rare entities with an estimated incidence of 10-25 per 100,000 inhabitants but the incidence greatly increases beyond the age of 65 years. The prognosis depends on the underlying cause. The fibrotic disorders show a set of radiological and histopathological patterns that are distinct but not entirely specific. In the absence of a clear clinical picture and consistent high resolution computed tomography (HRCT) findings, patients are advised to undergo surgical lung biopsies from two or three lung lobes (or transbronchial biopsies) to determine the histopathological pattern. The ILDs are differentiated into disorders of known causes (e.g. collagen vascular disease, drug-related), idiopathic interstitial pneumonia (IIP), granulomatous ILDs (e.g. sarcoidosis) and other forms of ILD (e.g. Langerhans' cell histiocytosis). The IIPs encompass idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, cryptogen organizing pneumonia, lymphocytic interstitial pneumonia and acute interstitial pneumonia. Additionally, a category of unclassified interstitial pneumonia exists. The pathologist has to recognize and address the histopathological pattern. In a multidisciplinary discussion the disorder is allocated to a clinicopathological entity and the histopathological pattern plays a major role in the classification of the entity. Recognition of the underlying pattern and the respective histopathological differential diagnoses is important as the therapy varies depending on the cause and ranges from elimination of the stimulus (if possible) to antifibrotic drug therapy up to preparation for lung transplantation.

  3. Autophagy in lung disease pathogenesis and therapeutics

    PubMed Central

    Ryter, Stefan W.; Choi, Augustine M.K.

    2015-01-01

    Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics. PMID:25617802

  4. Allergic dermatoses and respiratory diseases from reactive dyes.

    PubMed

    Estlander, T

    1988-05-01

    5 cases of occupational eczema, urticaria and respiratory disease from reactive dyes, occurring during 1977-1987, are reported. The patients, 4 men and 1 woman, were 24-52 years old when examined. They had been working in dye houses or textile plants, and had been exposed to reactive dyes for 8 months to 4 years before symptoms developed. Only 1 of the patients has been able to continue in the same occupation. On patch testing, the 4 patients with eczema reacted positively to 9 commercial dye powders. 2 patients reacted to the same dye, Remazol Schwarz B. On scratch and/or prick testing, the 2 patients who also had respiratory symptoms and/or urticaria reacted positively to the same dyes as on patch testing. The 5th patient, who had urticaria and respiratory symptoms, reacted positively to a dye, Remazol Gold Gelb RNL, but the patch test with that dye was negative. None of the patients was patch-test-positive to para-phenylenediamine (PPD) or to textile dye allergens in a series of organic dyes. Thus, the series of organic dyes has little value in the screening of allergy to reactive dyes. A 1% pet. dilution of commercial dye powder for patch testing and the same concentration in distilled water for prick testing seem to be suitable for the screening of allergy to reactive dyes.

  5. Quantitative Stratification of Diffuse Parenchymal Lung Diseases

    PubMed Central

    Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Maldonado, Fabien; Peikert, Tobias; Moua, Teng; Ryu, Jay H.; Bartholmai, Brian J.; Robb, Richard A.

    2014-01-01

    Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread pathological changes within the pulmonary tissue that impair the elasticity and gas exchange properties of the lungs. Clinical-radiological diagnosis of these diseases remains challenging and their clinical course is characterized by variable disease progression. These challenges have hindered the introduction of robust objective biomarkers for patient-specific prediction based on specific phenotypes in clinical practice for patients with DPLD. Therefore, strategies facilitating individualized clinical management, staging and identification of specific phenotypes linked to clinical disease outcomes or therapeutic responses are urgently needed. A classification schema consistently reflecting the radiological, clinical (lung function and clinical outcomes) and pathological features of a disease represents a critical need in modern pulmonary medicine. Herein, we report a quantitative stratification paradigm to identify subsets of DPLD patients with characteristic radiologic patterns in an unsupervised manner and demonstrate significant correlation of these self-organized disease groups with clinically accepted surrogate endpoints. The proposed consistent and reproducible technique could potentially transform diagnostic staging, clinical management and prognostication of DPLD patients as well as facilitate patient selection for clinical trials beyond the ability of current radiological tools. In addition, the sequential quantitative stratification of the type and extent of parenchymal process may allow standardized and objective monitoring of disease, early assessment of treatment response and mortality prediction for DPLD patients. PMID:24676019

  6. The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

    PubMed Central

    Kamaruzaman, Nurfatin Asyikhin; Kamaldin, Nurulain ‘Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham

    2013-01-01

    No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy. PMID:23653896

  7. Allergic reactions (image)

    MedlinePlus

    Allergic reaction is a sensitivity to a specific substance, called an allergen, that is contacted through the skin, inhaled into the lungs, swallowed or injected. The body's reaction to an allergen can be mild, such as ...

  8. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update

    PubMed Central

    Okada, H; Kuhn, C; Feillet, H; Bach, J-F

    2010-01-01

    According to the ‘hygiene hypothesis’, the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both autoimmune and allergic diseases. The hygiene hypothesis is based upon epidemiological data, particularly migration studies, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation. However, these data and others showing a correlation between high disease incidence and high socio-economic level do not prove a causal link between infections and immune disorders. Proof of principle of the hygiene hypothesis is brought by animal models and to a lesser degree by intervention trials in humans. Underlying mechanisms are multiple and complex. They include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These mechanisms could originate, to some extent, from changes in microbiota caused by changes in lifestyle, particularly in inflammatory bowel diseases. Taken together, these data open new therapeutic perspectives in the prevention of autoimmune and allergic diseases. PMID:20415844

  9. Allergen-specific immunotherapy: towards combination vaccines for allergic and infectious diseases.

    PubMed

    Edlmayr, Johanna; Niespodziana, Katarzyna; Focke-Tejkl, Margarete; Linhart, Birgit; Valenta, Rudolf

    2011-01-01

    IgE-mediated allergies affect more than 25% of the population. Allergen-specific immunotherapy (SIT) is an antigen-specific and disease-modifying form of treatment. It is based on the therapeutic administration of the disease-causing allergens to allergic patients. However, the fact that only allergen extracts of insufficient quality are currently available and the possible occurrence of side effects during treatment limit the broad use of SIT and prophylactic vaccination is has not yet been performed. In the last 20 years the DNA sequences of the most common allergens have been isolated and the corresponding allergens have been produced as recombinant allergens. Based on the progress made in the field of allergen characterization it is possible to improve the quality and safety of allergy vaccines and to develop new, more effective strategies for a broad application of SIT and even for prophylactic treatment. Here we discuss the development of combination vaccines for allergy and infectious diseases. This approach is based on the selection of allergen-derived peptides with reduced IgE- and T cell reactivity in order to minimize IgE- and T cell-mediated side effects as well as the potential of the vaccine to induce allergic sensitization. These peptides are fused by recombinant technology onto a viral carrier protein to obtain a combination vaccine which induces protective immunity against allergy and viral infections. The application of such combination vaccines for therapy and prophylaxis of allergy and infectious diseases is discussed.

  10. Long-lived Th2 memory in experimental allergic asthma.

    PubMed

    Mojtabavi, Nazanin; Dekan, Gerhard; Stingl, Georg; Epstein, Michelle M

    2002-11-01

    Although life-long immunity against pathogens is beneficial, immunological memory responses directed against allergens are potentially harmful. Because there is a paucity of information about Th2 memory cells in allergic disease, we established a model of allergic asthma in BALB/c mice to explore the generation and maintenance of Th2 memory. We induced disease without the use of adjuvants, thus avoiding Ag depots, and found that unlike allergic asthma in mice immunized with adjuvant, immunizing with soluble and aerosol OVA resulted in pathological lung lesions resembling human disease. To test memory responses we allowed mice with acute disease to recover and then re-exposed them to aerosol OVA a second time. Over 400 days later these mice developed OVA-dependent eosinophilic lung inflammation, airway hyperresponsiveness, mucus hypersecretion, and IgE. Over 1 year after recuperating from acute disease, mice had persistent lymphocytic lung infiltrates, Ag-specific production of IL-4 and IL-5 from spleen and lung cells in vitro, and elevated IgG1. Moreover, when recuperated mice were briefly aerosol challenged, we detected early expression of Th2 cytokine RNA in lungs. Taken together, these data demonstrate the presence of long-lived Th2 memory cells in spleen and lungs involved in the generation of allergic asthma upon Ag re-exposure.

  11. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

    PubMed

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis.

  12. Antioxidant vitamins and prevention of lung disease

    SciTech Connect

    Menzel, D.B. )

    1992-09-30

    Although the evidence for oxidative stress for air pollution in the human lung is fragmentary, the hypothesis that oxidative stress is an important, if not the sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is compelling and growing. First, biochemical mechanisms have been worked out for oxidation of lung lipids by the gas phase of cigarette smoke, NO[sub 2] and O[sub 3]. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO[sub 2], and vitamin E is more effective against O[sub 3]. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO[sub 2] and O[sub 3], respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO[sub 2] or O[sub 3] are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO[sub 2] and O[sub 3] by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO[sub 2] for short-term exposures or increases on chronic cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is apparently complex and may be related to the daily intake of vitamin C as well as smoking. Serum vitamin C levels may be poor indicators of lung demands when daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation protects against the effects of ambient levels of air pollution in adults as measured by histamine challenge. An augmented response to histamine challenge may represent increased lung permeability brought about by air pollution. In experimental animal and human experiments, the amount of vitamin C or E that afforded protection was in excess of the current recommended dietary allowance.

  13. Is Folate Status a Risk Factor for Asthma or Other Allergic Diseases?

    PubMed Central

    Wang, Ting; Zhang, Hong-Ping; Zhang, Xin; Liang, Zong-An; Ji, Yu-Lin

    2015-01-01

    Purpose It is controversial whether folate status is a risk factor for the development of asthma or other allergic diseases. This study was conducted to investigate whether indirect or direct exposure to folate and impaired folate metabolism, reflected as methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism, would contribute to the development of asthma and other allergic diseases. Methods Electronic databases were searched to identify all studies assessing the association between folate status and asthma or other allergic diseases. Two reviewers independently assessed the eligibility of studies and extracted data. The relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CI) was calculated and pooled. Results Twenty-six studies (16 cohort, 7 case-control, and 3 cross-sectional studies) were identified. Maternal folic acid supplementation was not associated with the development of asthma, atopic dermatitis (AD), eczema, and sensitization in the offspring, whereas exposure during early pregnancy was related to wheeze occurrence in the offspring (RR=1.06, 95% CI=[1.02-1.09]). The TT genotype of MTHFR C677T polymorphism was at high risk of asthma (OR=1.41, 95% CI=[1.07-1.86]). Conclusions It is indicated that maternal folic acid supplementation during early pregnancy may increase the risk of wheeze in early childhood and that the TT genotype of MTHFR C677T polymorphism impairing folic acid metabolism would be at high risk of asthma development. These results might provide additional information for recommendations regarding forced folate consumption or folic acid supplements during pregnancy based on its well-established benefits for the prevention of congenital malformations. However, currently available evidence is of low quality which is needed to further elucidate. PMID:26333700

  14. Interstitial lung disease in the connective tissue diseases.

    PubMed

    Antin-Ozerkis, Danielle; Rubinowitz, Ami; Evans, Janine; Homer, Robert J; Matthay, Richard A

    2012-03-01

    The connective tissue diseases (CTDs) are inflammatory, immune-mediated disorders in which interstitial lung disease (ILD) is common and clinically important. Interstitial lung disease may be the first manifestation of a CTD in a previously healthy patient. CTD-associated ILD frequently presents with the gradual onset of cough and dyspnea, although rarely may present with fulminant respiratory failure. Infection and drug reaction should always be ruled out. A diagnosis of idiopathic ILD should never be made without a careful search for subtle evidence of underlying CTD. Treatment of CTD-ILD typically includes corticosteroids and immunosuppressive agents.

  15. Presence of other allergic disease modifies the effect of early childhood traffic-related air pollution exposure on asthma prevalence.

    PubMed

    Dell, Sharon D; Jerrett, Michael; Beckerman, Bernard; Brook, Jeffrey R; Foty, Richard G; Gilbert, Nicolas L; Marshall, Laura; Miller, J David; To, Teresa; Walter, Stephen D; Stieb, David M

    2014-04-01

    Nitrogen dioxide (NO2), a surrogate measure of traffic-related air pollution (TRAP), has been associated with incident childhood asthma. Timing of exposure and atopic status may be important effect modifiers. We collected cross-sectional data on asthma outcomes from Toronto school children aged 5-9years in 2006. Lifetime home, school and daycare addresses were obtained to derive birth and cumulative NO2 exposures for a nested case-control subset of 1497 children. Presence of other allergic disease (a proxy for atopy) was defined as self-report of one or more of doctor-diagnosed rhinitis, eczema, or food allergy. Generalized estimating equations were used to adjust for potential confounders, and examine hypothesized effect modifiers while accounting for clustering by school. In children with other allergic disease, birth, cumulative and 2006 NO2 were associated with lifetime asthma (OR 1.46, 95% CI 1.08-1.98; 1.37, 95% CI 1.00-1.86; and 1.60, 95% CI 1.09-2.36 respectively per interquartile range increase) and wheeze (OR 1.44, 95% CI 1.10-1.89; 1.31, 95% CI 1.02-1.67; and 1.60, 95% CI 1.16-2.21). No or weaker effects were seen in those without allergic disease, and effect modification was amplified when a more restrictive algorithm was used to define other allergic disease (at least 2 of doctor diagnosed allergic rhinitis, eczema or food allergy). The effects of modest NO2 levels on childhood asthma were modified by the presence of other allergic disease, suggesting a probable role for allergic sensitization in the pathogenesis of TRAP initiated asthma.

  16. Adaptation to Impacts of Climate Change on Aeroallergens and Allergic Respiratory Diseases

    PubMed Central

    Beggs, Paul J.

    2010-01-01

    Climate change has the potential to have many significant impacts on aeroallergens such as pollen and mould spores, and therefore related diseases such as asthma and allergic rhinitis. This paper critically reviews this topic, with a focus on the potential adaptation measures that have been identified to date. These are aeroallergen monitoring; aeroallergen forecasting; allergenic plant management; planting practices and policies; urban/settlement planning; building design and heating, ventilating, and air-conditioning (HVAC); access to health care and medications; education; and research. PMID:20948943

  17. Adaptation to impacts of climate change on aeroallergens and allergic respiratory diseases.

    PubMed

    Beggs, Paul J

    2010-08-01

    Climate change has the potential to have many significant impacts on aeroallergens such as pollen and mould spores, and therefore related diseases such as asthma and allergic rhinitis. This paper critically reviews this topic, with a focus on the potential adaptation measures that have been identified to date. These are aeroallergen monitoring; aeroallergen forecasting; allergenic plant management; planting practices and policies; urban/settlement planning; building design and heating, ventilating, and air-conditioning (HVAC); access to health care and medications; education; and research. PMID:20948943

  18. RNAi Therapeutic Platforms for Lung Diseases

    PubMed Central

    Fujita, Yu; Takeshita, Fumitaka; Kuwano, Kazuyoshi; Ochiya, Takahiro

    2013-01-01

    RNA interference (RNAi) is rapidly becoming an important method for analyzing gene functions in many eukaryotes and holds promise for the development of therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are central to RNAi. Drug discovery studies and novel treatments of siRNAs are currently targeting a wide range of diseases, including various viral infections and cancers. Lung diseases in general are attractive targets for siRNA therapeutics because of their lethality and prevalence. In addition, the lung is anatomically accessible to therapeutic agents via the intrapulmonary route. Recently, increasing evidence indicates that miRNAs play an important role in lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are being targeted for therapeutic purposes. In this review, we present strategies for RNAi delivery and discuss the current state-of-the-art RNAi-based therapeutics for various lung diseases. PMID:24275949

  19. Restoring airway epithelial barrier dysfunction: a new therapeutic challenge in allergic airway disease.

    PubMed

    Steelant, B; Seys, S F; Boeckxstaens, G; Akdis, C A; Ceuppens, J L; Hellings, P W

    2016-09-01

    An intact functional mucosal barrier is considered to be crucial for the maintenance of airway homeostasis as it protects the host immune system from exposure to allergens and noxious environmental triggers. Recent data provided evidence for the contribution of barrier dysfunction to the development of inflammatory diseases in the airways, skin and gut. A defective barrier has been documented in chronic rhinosinusitis, allergic rhinitis, asthma, atopic dermatitis and inflammatory bowel diseases. However, it remains to be elucidated to what extent primary (genetic) versus secondary (inflammatory) mechanisms drive barrier dysfunction. The precise pathogenesis of barrier dysfunction in patients with chronic mucosal inflammation and its implications on tissue inflammation and systemic absorption of exogenous particles are only partly understood. Since epithelial barrier defects are linked with chronicity and severity of airway inflammation, restoring the barrier integrity may become a useful approach in the treatment of allergic diseases. We here provide a state-of-the-art review on epithelial barrier dysfunction in upper and lower airways as well as in the intestine and the skin and on how barrier dysfunction can be restored from a therapeutic perspective.

  20. Effects of exercise training on atrophy gene expression in skeletal muscle of mice with chronic allergic lung inflammation.

    PubMed

    Durigan, J L Q; Peviani, S M; Russo, T L; Silva, A C D; Vieira, R P; Martins, M A; Carvalho, C R F; Salvini, T F

    2009-04-01

    We evaluated the effects of chronic allergic airway inflammation and of treadmill training (12 weeks) of low and moderate intensity on muscle fiber cross-sectional area and mRNA levels of atrogin-1 and MuRF1 in the mouse tibialis anterior muscle. Six 4-month-old male BALB/c mice (28.5 +/- 0.8 g) per group were examined: 1) control, non-sensitized and non-trained (C); 2) ovalbumin sensitized (OA, 20 microg per mouse); 3) non-sensitized and trained at 50% maximum speed _ low intensity (PT50%); 4) non-sensitized and trained at 75% maximum speed _ moderate intensity (PT75%); 5) OA-sensitized and trained at 50% (OA+PT50%), 6) OA-sensitized and trained at 75% (OA+PT75%). There was no difference in muscle fiber cross-sectional area among groups and no difference in atrogin-1 and MuRF1 expression between C and OA groups. All exercised groups showed significantly decreased expression of atrogin-1 compared to C (1.01 +/- 0.2-fold): PT50% = 0.71 +/- 0.12-fold; OA+PT50% = 0.74 +/- 0.03-fold; PT75% = 0.71 +/- 0.09-fold; OA+PT75% = 0.74 +/- 0.09-fold. Similarly significant results were obtained regarding MuRF1 gene expression compared to C (1.01 +/- 0.23-fold): PT50% = 0.53 +/- 0.20-fold; OA+PT50% = 0.55 +/- 0.11-fold; PT75% = 0.35 +/- 0.15-fold; OA+PT75% = 0.37 +/- 0.08-fold. A short period of OA did not induce skeletal muscle atrophy in the mouse tibialis anterior muscle and aerobic training at low and moderate intensity negatively regulates the atrophy pathway in skeletal muscle of healthy mice or mice with allergic lung inflammation.

  1. Application of statistical mining in healthcare data management for allergic diseases

    NASA Astrophysics Data System (ADS)

    Wawrzyniak, Zbigniew M.; Martínez Santolaya, Sara

    2014-11-01

    The paper aims to discuss data mining techniques based on statistical tools in medical data management in case of long-term diseases. The data collected from a population survey is the source for reasoning and identifying disease processes responsible for patient's illness and its symptoms, and prescribing a knowledge and decisions in course of action to correct patient's condition. The case considered as a sample of constructive approach to data management is a dependence of allergic diseases of chronic nature on some symptoms and environmental conditions. The knowledge summarized in a systematic way as accumulated experience constitutes to an experiential simplified model of the diseases with feature space constructed of small set of indicators. We have presented the model of disease-symptom-opinion with knowledge discovery for data management in healthcare. The feature is evident that the model is purely data-driven to evaluate the knowledge of the diseases` processes and probability dependence of future disease events on symptoms and other attributes. The example done from the outcomes of the survey of long-term (chronic) disease shows that a small set of core indicators as 4 or more symptoms and opinions could be very helpful in reflecting health status change over disease causes. Furthermore, the data driven understanding of the mechanisms of diseases gives physicians the basis for choices of treatment what outlines the need of data governance in this research domain of discovered knowledge from surveys.

  2. [Lung Cancer as an Occupational Disease].

    PubMed

    Baur, X; Woitowitz, H-J

    2016-08-01

    Lung cancer is one of the most frequently encountered cancer types. According to the latest WHO data, about 10 % of this disease are due to occupational exposure to cancerogens. Asbestos is still the number one carcinogen. Further frequent causes include quarz and ionizing radiation (uranium mining). Probable causes of the disease can be identified only with the help of detailed occupational history taken by a medical specialist and qualified exposure assessment. Without clarifying the cause of the disease, there is neither a correct insurance procedure nor compensation for the victim, and furthermore, required preventive measures cannot be initiated. PMID:27512930

  3. Gastroesophageal Reflux Disease in Children with Interstitial Lung Disease.

    PubMed

    Dziekiewicz, M A; Karolewska-Bochenek, K; Dembiński, Ł; Gawronska, A; Krenke, K; Lange, J; Banasiuk, M; Kuchar, E; Kulus, M; Albrecht, P; Banaszkiewicz, A

    2016-01-01

    Gastroesophageal reflux disease is common in adult patients with interstitial lung disease. However, no data currently exist regarding the prevalence and characteristics of the disease in pediatric patients with interstitial lung disease. The aim of the present study was to prospectively assess the incidence of gastroesophageal reflux disease and characterize its features in children with interstitial lung disease. Gastroesophageal reflux disease was established based on 24 h pH-impedance monitoring (MII-pH). Gastroesophageal reflux episodes (GERs) were classified according to widely recognized criteria as acid, weakly acid, weakly alkaline, or proximal. Eighteen consecutive patients (15 boys, aged 0.2-11.6 years) were enrolled in the study. Gastroesophageal reflux disease was diagnosed in a half (9/18) of children. A thousand GERs were detected by MII-pH (median 53.5; IQR 39.0-75.5). Of these, 585 (58.5 %) episodes were acidic, 407 (40.7 %) were weakly acidic, and eight (0.8 %) were weakly alkaline. There were 637 (63.7 %) proximal GERs. The patients in whom gastroesophageal reflux disease was diagnosed had a significantly higher number of proximal and total GERs. We conclude that the prevalence of gastroesophageal reflux disease in children with interstitial lung disease is high; thus, the disease should be considered regardless of presenting clinical symptoms. A high frequency of non-acid and proximal GERs makes the MII-pH method a preferable choice for the detection of reflux episodes in this patient population. PMID:27068927

  4. [Real effect of specific hyposensitisation in therapy of allergic respiratory diseases].

    PubMed

    Plavsić, Z; Petrović, M; Popovac, D

    1994-01-01

    There are different opinions on the positive effect of hyposensitisation in the treatment of allergic respiratory diseases. In this paper we wish to point out our experience, without intention to clear up these "contrary opinions". Sixty patients of both sexes, aged from 10-55 years, were on specific hyposensitisation over a period from three to five years. Two thirds (63%) were with bronchial asthma and 37% with allergic rhinitis. Most of them (80%) were on specific hyposensitisation to one allergen (Dermatophagoides pteronyssinus, grass or reguid polen), and to two allergens 20% patients. During this therapy 63% of patients had no additional medicamentae therapy. Most of them stopped additional medication during the first year of immunotherapy. Ten percent of patients took medicaments when they needed them, and 28% took them continually. Clinical symptoms characteristic of these diseases were also rare. The average value of IgE was 636 UI/ml before and 341 UI/ml after the immunotherapy. The efficacy of immunotherapy depended on the correct selection of patients, good standardisation of antigen extract, and a right dose of allergen in the prolonged immunotherapy. PMID:17974388

  5. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

  6. The genetics of asthma and allergic disease: a 21st century perspective.

    PubMed

    Ober, Carole; Yao, Tsung-Chieh

    2011-07-01

    Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell-derived cytokines, interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL-33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T-helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSDML genes, is specifically associated with risk for childhood onset asthma. These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits. PMID:21682736

  7. Probiotic lactic acid bacteria and their potential in the prevention and treatment of allergic diseases

    PubMed Central

    Wróblewska, Paula; Adamczuk, Piotr; Silny, Wojciech

    2014-01-01

    Allergy is one of the most important and very common health problems worldwide. To reduce the proportion of people suffering from allergy, alternative methods of prevention and treatment are sought. The aim of this paper is to present the possibilities of probiotics in the prevention and treatment of allergic diseases. Probiotics are live microorganisms belonging mainly to the lactic acid bacteria. They modify the microflora of the human digestive system, especially the intestinal microflora. Prophylactic administration of probiotics in the early stages of life (naturally in breast milk or milk substitute synthetic compounds) is very important because intestinal microflora plays a huge role in the development of the immune system. Prevention of allergies as early as in the prenatal and postnatal periods provides huge opportunities for inhibiting the growing problem of allergy in emerging and highly developed societies. Effects of probiotic therapy depend on many factors such as the species of the microorganism used, the dose size and characteristics of the bacteria such as viability and capacity of adhesion to the intestinal walls. Authors of several studies showed beneficial effects of probiotics in the perinatal period, infancy, and also in adults in the prevention of atopic dermatitis or allergic rhinitis. Probiotics, due to their immunomodulatory properties and safety of use are a good, natural alternative for the prevention and treatment of many diseases including allergies. It is therefore important to explore the knowledge about their use and to carry out further clinical trials. PMID:26155109

  8. Allergic inflammation: where epithelial function interacts with immune response in atopic diseases.

    PubMed

    Godoy, Laura

    2009-05-01

    Current hot topics in allergy and asthma were presented this year at the annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in Washington, D.C. Understanding the natural history of allergic diseases is an area of interest because it could help to identify relevant biomarkers to predict allergy early in infancy. An abnormal epithelial barrier allows easy access to allergens/ pathogens and such a dysfunction could also be involved in the initiation of the natural course of allergic diseases. In addition, newly identified cytokines produced by epithelial cells such as thymic stromal lymphopoietin, interleukin-33 (IL-33) and IL-25 are involved in the generation of T helper type 2 (Th2) cell response. Genetic studies are also providing relevant information on biomarkers and new targets for allergy and asthma. Different genetic studies to identify single nucleotide polymorphisms of relevant mediators of allergy in patients, application of gene array analysis to identify biomarkers during asthma exacerbation, and IL-13-induced inflammatory events, are some examples of the interesting information presented at the AAAAI this year.

  9. Comparison of breast, cow, and soy feedings in the prevention of onset of allergic disease: a 15-year prospective study.

    PubMed

    Gruskay, F L

    1982-08-01

    It has been reported that the feeding of cow's milk may enhance the development of atopy in predisposed infants. A prospective study following children from birth through 15 years of age in a private pediatric practice was designed to determine if the food ingested during the first months of life is related to the development of atopy in the offspring of allergic families. Each of 328 children with a positive family history of allergy was assigned to one of three groups according to the feeding preference of the parents: 48 were fed breast milk; 79 soy-based formula; and 201, cow's milk formula. All groups had egg, citrus, tomato, and wheat restrictions as well as inhalant allergen avoidance. These were compared to a control group of 580 children with no family history of allergy. Breast fed infants were found to have approximately one-half the incidence of atopy of cow's milk or soy formula fed infants from atopic families when followed for up to 15 years. Soy feeding produced no advantage over cow's milk in the prophylaxis of allergic disease. There was a three-fold increase in clinically apparent atopic disease in offspring of allergic families when compared to controls but only a two-fold increase if the infant was breast fed. These results support the hypothesis that breast feeding and delay of exposure to known allergens may reduce the frequency of clinical allergic disease in the offspring of allergic families.

  10. Effects of allergic diseases and age on the composition of serum IgG glycome in children.

    PubMed

    Pezer, Marija; Stambuk, Jerko; Perica, Marija; Razdorov, Genadij; Banic, Ivana; Vuckovic, Frano; Gospic, Adrijana Miletic; Ugrina, Ivo; Vecenaj, Ana; Bakovic, Maja Pucic; Lokas, Sandra Bulat; Zivkovic, Jelena; Plavec, Davor; Devereux, Graham; Turkalj, Mirjana; Lauc, Gordan

    2016-01-01

    It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients' IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children's Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children. PMID:27616597

  11. Effects of allergic diseases and age on the composition of serum IgG glycome in children

    PubMed Central

    Pezer, Marija; Stambuk, Jerko; Perica, Marija; Razdorov, Genadij; Banic, Ivana; Vuckovic, Frano; Gospic, Adrijana Miletic; Ugrina, Ivo; Vecenaj, Ana; Bakovic, Maja Pucic; Lokas, Sandra Bulat; Zivkovic, Jelena; Plavec, Davor; Devereux, Graham; Turkalj, Mirjana; Lauc, Gordan

    2016-01-01

    It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients’ IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children’s Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children. PMID:27616597

  12. [Value of the study of the functional potential of neutrophils in suppurative, septic and allergic diseases in children].

    PubMed

    Nesterova, I V; Svetlichnaia, M A

    1989-01-01

    A method for measuring the content of cationic proteins in neutrophil granulocytes of the peripheral blood was employed in patients with pyoseptic (n = 12) and allergic (n = 28) diseases during the exposure to composite infections in vitro. The method enables one to assess the functional potentialities of the cells in mobilizing the internal reserves and the readiness for the trigger of the cellular granular apparatus, for instance during real or predicted exposure of the child to bacterial infections. The determination of the functional potentialities of neutrophil phagocytes can be used as a test for the appraisal of the gravity of allergic and pyoseptic processes as well as for predicting outcomes of pyoseptic diseases.

  13. [Relationship of the ambient air concentrations of chemical substances to the spread of allergic diseases in children].

    PubMed

    Galeev, K A; Khakimova, R F

    2002-01-01

    The role of some ingredients that contaminate the ambient air in the occurrence and development of allergic diseases was studied. The closest relationships were found between the concentrations of hydrogen sulfide and the prevalence of eczema (rxy +/- m = 0.48 +/- 0.15). There was a direct correlation between the concentrations of each ingredient and the incidence of neurodermitis among children. The correlation between the summarized concentrations of ingredients and the incidence of bronchial asthma among children was rxy +/- m = 0.71 +/- 0.19. The findings serves as the basis for elaborating measures to reduce ecological tension and the incidence of allergic diseases in children. PMID:12380496

  14. Zinc oxide nanoparticles, a novel candidate for the treatment of allergic inflammatory diseases.

    PubMed

    Kim, Min-Ho; Seo, Jun-Ho; Kim, Hyung-Min; Jeong, Hyun-Ja

    2014-09-01

    Zinc (Zn) is an essential trace metal for eukaryotes. The roles of Zn in the numerous physiological functions have been elucidated. Bamboo salt contains Zn that was shown to have anti-inflammatory effect and other health benefits. Nanoparticles of various types have found application in the biology, medicine, and physics. Here we synthesized tetrapod-like, zinc oxide nanoparticles (ZO-NP; diameter 200 nm, source of Zn) using a radio frequency thermal plasma system and investigated its effects on mast cell-mediated allergic inflammatory reactions. ZO-NP was found to inhibit the productions and mRNA expressions of inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α on the phorbol 12-myristate 13-acetate plus A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells. In these stimulated cells, caspase-1 and nuclear factor-κB activations were abolished by ZO-NP, and the expressions of receptor interacting protein2 (RIP2) and IκB kinaseβ (IKKβ) induced by PAMCI were reduced. On the other hand, ZO-NP alone increased the expressions of RIP2 and IKKβ in normal condition. ZO-NP inhibited the phosphorylation of extracellular signal-regulated protein kinase in the PMACI-stimulated HMC-1 cells. Furthermore, ZO-NP significantly inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. These findings indicate that ZO-NP effectively ameliorates mast cell-mediated allergic inflammatory reaction, and suggest that ZO-NP be considered a potential therapeutic for the treatment of mast cell-mediated allergic diseases.

  15. Pulmonary hypertension in chronic lung diseases.

    PubMed

    Seeger, Werner; Adir, Yochai; Barberà, Joan Albert; Champion, Hunter; Coghlan, John Gerard; Cottin, Vincent; De Marco, Teresa; Galiè, Nazzareno; Ghio, Stefano; Gibbs, Simon; Martinez, Fernando J; Semigran, Marc J; Simonneau, Gerald; Wells, Athol U; Vachiéry, Jean-Luc

    2013-12-24

    Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on

  16. Effect of dexamethasone and Nigella sativa on inducible nitric oxide synthase in the lungs of a murine model of allergic Asthma.

    PubMed

    Abdel-Aziz, Mohamed; Abass, Ayman; Zalata, Khaled; Abd Al-Galel, Tarek; Allam, Umamma; Karrouf, Gamal

    2014-10-01

    The aim of this study was to investigate the effects of Nigella sativa (NS) fixed oil in comparison to dexamethasone (Dex) on inducible nitric oxide synthase (iNOS), peripheral blood eosinophils (PBE), allergen specific serum IgG1 and interleukins and airway inflammation in a murine model of allergic asthma. Thirty-one mice were divided into four groups. Group I (n = 6) served as the control group. Group II (n = 10) mice were sensitized intraperitoneally and challenged intratracheally with cone albumin with no treatment. Group III(n = 6) mice were sensitized, challenged, and treated with Dex for 17 days starting at 24 hours after the first challenge. Group IV (n = 9) mice were sensitized, challenged, and treated with NS fixed oil for 17 days as well. For all groups, the following procedures were carried out: immunohistochemical study of iNOS in lung tissues, detection of PBE percentage, and histopathological examination of lung tissues for inflammatory cells. Lung tissue iNOS expression increased in sensitized, non-treated mice compared with controls, but this increase was not significant. NS fixed oil treatment significantly reduced PBE and lung inflammation but did not significantly reduce lung tissue iNOS expression compared with the control group. These effects were comparable to the effects of Dex. These results suggest that Nigella sativa exhibits immunomodulatory and anti-inflammatory effect which may be useful for treatment of allergic asthma. PMID:25150073

  17. Subcutaneous allergen immunotherapy for allergic disease: examining efficacy, safety and cost-effectiveness of current and novel formulations.

    PubMed

    Cox, Linda; Calderón, Moisés; Pfaar, Oliver

    2012-06-01

    Subcutaneous immunotherapy (SCIT) is a unique therapy for allergic disease because it provides symptomatic relief while modifying the allergic disease by targeting the underlying immunological mechanism. Its efficacy and safety have been established in the treatment of asthma, allergic rhinitis/rhinoconjunctivitis and stinging insect hypersensitivity in numerous controlled clinical trials. This review evaluates a spectrum of clinical factors, ranging from efficacy to cost-effectiveness, which should be considered in evaluating SCIT. The evidence for SCIT safety and efficacy for these conditions is reviewed in an evaluation of the systematic reviews and meta-analyses. The evidence for the persistent and preventive effects of SCIT is also examined. An overview of the SCIT outcomes measures utilized in clinical trials is presented. The cost-effectiveness of SCIT compared with conventional medication treatment, novel indications and formulations for SCIT are also explored in this review. PMID:22788128

  18. Dietary prevention of allergic diseases in infants and small children. Part I: immunologic background and criteria for hypoallergenicity.

    PubMed

    Muraro, Antonella; Dreborg, Sten; Halken, Susanne; Høst, Arne; Niggemann, Bodo; Aalberse, Rob; Arshad, Syed H; Berg Av, Andrea von; Carlsen, Kai- Hå kon; Duschén, Karel; Eigenmann, Philippe; Hill, David; Jones, Catherine; Mellon, Michael; Oldeus, Göran; Oranje, Arnold; Pascual, Cristina; Prescott, Susan; Sampson, Hugh; Svartengren, Magnus; Vandenplas, Yvan; Wahn, Ulrich; Warner, Jill A; Warner, John O; Wickman, Magnus; Zeiger, Robert S

    2004-04-01

    The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.

  19. Nilotinib-induced interstitial lung disease.

    PubMed

    Go, Se-Il; Lee, Won Sup; Lee, Gyeong-Won; Kang, Jung Hun; Kang, Myung Hee; Lee, Jeong-Hee; Kim, Hoon-Gu

    2013-09-01

    Nilotinib is a second-generation tyrosine kinase inhibitor active in patients with chronic myeloid leukemia (CML) resistant to imatinib, and has been recently approved for newly diagnosed patients. We present a case of nilotinib-induced interstitial lung disease (ILD). A 67-year-old female patient was initially treated with imatinib for chronic-phase Philadelphia chromosome-positive (Ph(+)) CML. Imatinib was replaced by nilotinib because of hematological toxicity. The patient had received nilotinib for about 3 years without significant adverse effects. She visited the clinic due to chronic cough; chest X-ray revealed consolidations in both lung fields. Nilotinib-induced ILD was diagnosed based on intensive workup, including lung biopsy. She responded dramatically to corticosteroid therapy. To our knowledge, this is the first reported case of nilotinib-induced ILD in a patient with Ph(+) CML. We emphasize that if unexplained lung abnormalities progress in patients receiving nilotinib, physicians should consider this potentially fatal complication in their differential diagnoses.

  20. Modulation of the immune response by infection with Cryptosporidium spp. in children with allergic diseases.

    PubMed

    Guangorena-Gómez, J O; Maravilla-Domínguez, A; García-Arenas, G; Cervantes-Flores, M; Meza-Velázquez, R; Rivera-Guillén, M; Acosta-Saavedra, L C; Goytia-Acevedo, R C

    2016-08-01

    It has been demonstrated that the allergic response can be ameliorated by the administration of pathogen derivatives that activate Toll-like receptors and induce a Th1-type immune response (IR). Cryptosporidium is a parasite that promotes an IR via Toll-like receptors and elicits the production of Th1-type cytokines, which limit cryptosporidiosis. The aim of this study was to investigate allergy-related immune markers in children naturally infected with Cryptosporidium. In a cross-sectional study, 49 children with or without clinical diagnosis of allergies, oocysts of Cryptosporidium spp. in the faeces were screened microscopically. We microscopically screened for leucocytes, examined T and B cells for allergy-related activation markers using flow cytometry and evaluated serum for total IgE using chemiluminescence. Children with allergies and Cryptosporidium in the faeces had significantly lower levels of total IgE, B cells, CD19(+) CD23(+) and CD19(+) CD124(+) cells as well as a greater percentage of interferon-gamma (IFN-γ(+) ) and IL-4(+) CD4(+) cells than children with allergies without Cryptosporidium. This is the first description of the modulation of the IR in children with allergic diseases in the setting of natural Cryptosporidium infection. Our findings suggest the involvement of CD4(+) cells producing IL-4 and IFN-γ in the IR to Cryptosporidium in naturally infected children. PMID:27150641

  1. Oral immunotherapy for allergic diseases using transgenic rice seeds: current state and future prospects.

    PubMed

    Saeki, Mayumi; Nishimura, Tomoe; Kaminuma, Osamu; Mori, Akio; Hiroi, Takachika

    2013-01-01

    Allergen-specific immunotherapy (IT) has been shown to provide clinical benefit for patients with allergic diseases. At present, subcutaneous and sublingual ITs are mainly authorized for clinical treatment. Oral administration of allergens seems to be the easiest way to achieve IT, though it has yet to be translated to the clinical setting, mainly due to the requirement of a large amount of allergens. Plants, especially rice seeds, have recently been recognized as superior allergen carriers for oral administration, because of their high productivity, stability and safety. Therefore, in order to establish clinically applicable oral IT, we have been developing transgenic rice seeds (Tg rice), in which major epitopes of cedar pollen allergens or house-dust mites (HDM) are expressed. The efficacy of this orally administered Tg rice was confirmed in murine models of allergic rhinitis and bronchial asthma. In the safety study of the Tg rice, no adverse effects on cynomolgus macaques were observed. In this review, we summarized the current state and future prospects of allergen-specific IT, focusing particularly on oral IT with allergen-expressing Tg rice.

  2. Arsenic and non-malignant lung disease.

    PubMed

    Guha Mazumder, D N

    2007-10-01

    Many aquifers in various parts of the world have been found to be contaminated with arsenic at concentration above 0.05 mg/L. However reports of large number of affected people in India and Bangladesh are unprecedented. Characteristic skin lesions (pigmentation, depigmentation and keratosis) are the hallmark signs of chronic arsenic toxicity. Emerging evidences show that ingestion of arsenic through drinking water may also lead to non-malignant respiratory effects. Early report of non-malignant pulmonary effect of chronic ingestion of arsenic was available from studies in children in Chile as early as 1970. However on the basis of case studies, respiratory effect of chronic arsenic toxicity in adults following drinking of arsenic contaminated water in West Bengal was first reported in 1997. Epidemiological studies carried out in West Bengal on a population of 7683 showed that the prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic induced skin lesions who also had high levels of arsenic in their current drinking water source (> or = 0.5 mg/L) compared with individuals who had normal skin and were exposed to low levels of arsenic (< 0.05 mg/L). In participants with skin lesions, age-adjusted POR estimates for chronic cough were 7.8 for females (95% CI:3.1-19.5) and 5.0 for males (95% CI:2.6-9.9). In Bangladesh, similar study carried out on a population of 218 showed that the crude prevalence ratio for chronic bronchitis was found to be 10.3 (95% CI:2.4-43.1) for females and 1.6 (95% CI:0.8-3.1) for males. Reports of lung function tests were available from both hospital and population based studies. Results show evidences of restrictive, obstructive and combined obstructive and restrictive lung disease in different people having chronic lung disease associated with chronic arsenic toxicity. On the basis of clinical study, chest X-ray and HRCT done in Arsenicosis patients with features of chronic lung disease, the abnormalities

  3. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer

    PubMed Central

    Hong, Su Jin; Kim, Tae Jung; Lee, Jae-Ho; Park, Jeong-Soo

    2016-01-01

    Abstract To describe the features and clinical implications of computed tomography (CT), positron emission tomography (PET), and percutaneous needle aspiration biopsy (PCNB) in pulmonary nontuberculous mycobacterial (NTM) disease manifesting as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. Among a cohort of 388 patients with NTM pulmonary disease, 14 patients with clinically and radiologically suspected lung cancer were included in our study. Two chest radiologists evaluated CT features, including lesion type (nodule, mass, or mass-like consolidation), morphologic features (margin, degree of enhancement, calcification), and presence of accompanying findings suggestive of NTM pulmonary disease (bronchiectasis with clustered centrilobular nodules or upper-lobe cavitary lesions) by consensus. Diagnostic procedures for microbiologic diagnosis of NTM disease and clinical outcome were reviewed. Incidence of NTM pulmonary disease presenting as solitary nodule/mass (n = 8) or mass-like consolidation (n = 6) was 3.6% (14 of 388). Most lesions were detected incidentally during routine health check-up or evaluation of other disease (11 of 14, 79%). Lesions typically showed poor contrast-enhancement (9 of 12) and internal calcification (6 of 14). No lesions had CT features suggestive of NTM pulmonary disease. All 4 lesions for which PET/CT imaging was performed showed strong fluorodeoxyglucose uptake simulating malignant lesions (mean, 4.9; range, 3.6–7.8). PCNB revealed mycobacterial histology in 6 of 11 specimens and positive culture results were obtained for 7 of 7 specimens. NTM pulmonary disease may present as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. CT features and PCNB are important to diagnose NTM disease mimicking lung cancer to avoid unnecessary surgery. PMID:27367996

  4. Pulmonary hypertension in chronic interstitial lung diseases.

    PubMed

    Caminati, Antonella; Cassandro, Roberto; Harari, Sergio

    2013-09-01

    Pulmonary hypertension (PH) is a common complication of interstitial lung diseases (ILDs), particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. The degree of PH in ILDs is typically mild-to-moderate. However, some of these patients may develop a disproportionate increase in PH that cannot be justified solely by hypoxia and parenchymal injury: this condition has been termed "out-of-proportion" PH. The pathogenesis of PH in these diseases is various, incompletely understood and may be multifactorial. The clinical suspicion (i.e. increased dyspnoea, low diffusion capacity) and echocardiographic assessment are the first steps towards proper diagnosis of PH; however, right heart catheterisation remains the current gold standard for diagnosis of PH. At present, no specific therapies have been approved for the treatment of PH in patients with ILDs. PMID:23997057

  5. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease

    PubMed Central

    2016-01-01

    Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed. PMID:27134484

  6. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

    PubMed

    Morris, Abigail; Wang, Bo; Waern, Ida; Venkatasamy, Radhakrishnan; Page, Clive; Schmidt, Eric P; Wernersson, Sara; Li, Jin-Ping; Spina, Domenico

    2015-01-01

    Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/-) mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT) control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil) recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD) found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

  7. Impaired induction of allergic lung inflammation by Alternaria alternata mutant MAPK homologue Fus3.

    PubMed

    Kim, Hee-Kyoo; Baum, Rachel; Lund, Sean; Khorram, Naseem; Yang, Siwy Ling; Chung, Kuang-Ren; Doherty, Taylor A

    2013-11-01

    The fungal allergen Alternaria alternata is associated with development of asthma, though the mechanisms underlying the allergenicity of Alternaria are largely unknown. The aim of this study was to identify whether the MAP kinase homologue Fus3 of Alternaria contributed to allergic airway responses. Wild-type (WT) and Fus3 deficient Alternaria extracts were given intranasal to mice. Extracts from Fus3 deficient Alternaria that had a functional copy of Fus3 introduced were also administered (CpFus3). Mice were challenged once and levels of BAL eosinophils and innate cytokines IL-33, thymic stromal lymphopoeitin (TSLP), and IL-25 (IL-17E) were assessed. Alternaria extracts or protease-inhibited extract were administered with (OVA) during sensitization prior to ovalbumin only challenges to determine extract adjuvant activity. Levels of BAL inflammatory cells, Th2 cytokines, and OX40-expressing Th2 cells as well as airway infiltration and mucus production were measured. WT Alternaria induced innate airway eosinophilia within 3 days. Mice given Fus3 deficient Alternaria were significantly impaired in developing airway eosinophilia that was largely restored by CpFus3. Further, BAL IL-33, TSLP, and Eotaxin-1 levels were reduced after challenge with Fus3 mutant extract compared with WT and CpFus3 extracts. WT and CpFus3 extracts demonstrated strong adjuvant activity in vivo as levels of BAL eosinophils, Th2 cytokines, and OX40-expressing Th2 cells as well as peribronchial inflammation and mucus production were induced. In contrast, the adjuvant activity of Fus3 extract or protease-inhibited WT extract was largely impaired. Finally, protease activity and Alt a1 levels were reduced in Fus3 mutant extract. Thus, Fus3 contributes to the Th2-sensitizing properties of Alternaria.

  8. Unclassifiable interstitial lung disease: A review.

    PubMed

    Skolnik, Kate; Ryerson, Christopher J

    2016-01-01

    Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD.

  9. Rare lung diseases II: Pulmonary alveolar proteinosis

    PubMed Central

    Juvet, Stephen C; Hwang, David; Waddell, Thomas K; Downey, Gregory P

    2008-01-01

    The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP), a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed. PMID:18551202

  10. Unclassifiable interstitial lung disease: A review.

    PubMed

    Skolnik, Kate; Ryerson, Christopher J

    2016-01-01

    Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD. PMID:26059704

  11. Acute exacerbations of fibrotic interstitial lung disease.

    PubMed

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

  12. [Choice of an antihistamine administration route in the treatment of allergic diseases].

    PubMed

    Luss, L V

    2016-01-01

    Allergic diseases (AD) are an interdisciplinary problem in practical health care and characterized by high prevalence, severity, and huge financial costs of their treatment, prevention, and rehabilitation in patients. In this connection, control of allergy symptoms attracts the meticulous attention of physicians of all specialties. The efficiency of pharmacotherapy in clinical practice frequently depends not only on what medication, but also what mode of its delivery (administration) is used. Clinicians are well aware of the fact that oral administration of some drugs, antihistamines in particular, may be lowly effective or ineffective and their parenteral route gives rise to their sufficient clinical effect. This communication presents for general practitioners a pathogenetic rationale for prescribing histamines and indications for their parenteral administration in AD. PMID:27030338

  13. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases.

    PubMed

    Boucher, Richard C

    2015-11-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency.

  14. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases

    PubMed Central

    2015-01-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency. PMID:26595733

  15. Therapeutic effect of 0.1% Tacrolimus Eye Ointment in Allergic Ocular Diseases

    PubMed Central

    Shitole, Satish C; Bhagat, Nupur; Patil, Deepak; Sawant, Pawan; Patil, Kalpita

    2016-01-01

    Introduction Allergic Ocular Diseases (AODs) like Atopic Keratoconjunctivitis (AKC) and Vernal Keratoconjunctivitis (VKC) are chronic forms of ocular allergy that can cause severe visual complications. Pathogenesis of AODs is uncertain and treatment has been a challenge for ophthalmologists. Tacrolimus, a 23-member cyclic macrolide lactone derived from [streptomyces tsukubaensis] now in ointment form has been successfully used in AODs. Aim To study the therapeutic effect of 0.1% Tacrolimus eye ointment in patients with Allergic Ocular Diseases (AODs). Materials and Methods This prospective observational study was conducted on 36 patients with severe AOD and moderate cases not responding to conventional treatment. They were treated with 0.1% tacrolimus eye ointment twice daily for minimum three months in addition to conventional treatment and observed for a period of 6 months. Symptoms and signs after treatment were evaluated. Grades of clinical signs were assessed based on slit lamp clinical photographs; development of possible complications was assessed and analysed by Wilcoxon signed rank test. Results Mean age of patients was 9.3±4.3 years and mean duration of AODs was 3.1±1.8 years. The scores on both the four point scales for signs and symptoms decreased significantly (p<0.0001) after 1 month of 0.1% Tacrolimus eye ointment treatment. Itching was the first symptom to show dramatic relief and conjunctival hyperaemia was the first sign to show improvement. 88.88% of patients were successfully weaned off topical steroids in 6 months into Tacrolimus treatment. Even in patients unresponsive to 0.1% topical Cyclosporine, symptoms and signs scores decreased significantly (p<0.0001). The most common adverse reaction was a transient burning sensation (36.11%). Conclusion Topical 0.1% Tacrolimus eye ointment was found to be a safe and effective treatment in cases of AODs and also worked as steroid sparing and replacing agent. It was also found effective in patient

  16. The gut microbiota and its role in the development of allergic disease: a wider perspective.

    PubMed

    West, C E; Jenmalm, M C; Prescott, S L

    2015-01-01

    The gut microbiota are critical in the homoeostasis of multiple interconnected host metabolic and immune networks. If early microbial colonization is delayed, the gut-associated lymphoid tissues (GALT) fail to develop, leading to persistent immune dysregulation in mice. Microbial colonization has also been proposed as a major driver for the normal age-related maturation of both Th1 and T regulatory (Treg) pathways that appear important in suppressing early propensity for Th2 allergic responses. There is emerging evidence that resident symbionts induce tolerogenic gut-associated Treg cells and dendritic cells that ensure the preferential growth of symbionts; keeping pathogenic strains in check and constraining proinflammatory Th1, Th2, and Th17 clones. Some effects of symbionts are mediated by short-chain fatty acids, which play a critical role in mucosal integrity and local and systemic metabolic function and stimulate the regulatory immune responses. The homoeostatic IL-10/TGF-β dominated tolerogenic response within the GALT also signals the production of secretory IgA, which have a regulating role in mucosal integrity. Contrary to the 'sterile womb' paradigm, recent studies suggest that maternal microbial transfer to the offspring begins during pregnancy, providing a pioneer microbiome. It is likely that appropriate microbial stimulation both pre- and postnatally is required for optimal Th1 and Treg development to avoid the pathophysiological processes leading to allergy. Disturbed gut colonization patterns have been associated with allergic disease, but whether microbial variation is the cause or effect of these diseases is still under investigation. We are far from understanding what constitutes a 'healthy gut microbiome' that promotes tolerance. This remains a major limitation and might explain some of the inconsistency in human intervention studies with prebiotics and probiotics. Multidisciplinary integrative approaches with researchers working in networks

  17. Allergic rhinitis

    MedlinePlus

    ... allergic to, such as dust, animal dander, or pollen. Symptoms can also occur when you eat a ... article focuses on allergic rhinitis due to plant pollens. This type of allergic rhinitis is commonly called ...

  18. Macrophage polarization in interstitial lung diseases

    PubMed Central

    Mierzejewski, Michał; Osińska, Iwona; Domagała-Kulawik, Joanna

    2016-01-01

    The role of bronchoalveolar lavage fluid (BALf) examination in differential diagnosis of interstitial lung diseases (ILD) was established. Currently, functional polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) subpopulations is emphasized. The aim of our study was to compare the proportion of M1 and M2 in BALf of patients with different ILD. BALf samples were collected from 75 ILD patients: sarcoidosis (SA, 36), hypersensitivity pneumonitis (HP, 10), non-specific interstitial pneumonia (NSIP, 8), idiopathic pulmonary fibrosis (IPF, 6) and other ILD (15). Phenotyping was performed by immunocytochemistry with anti-CD40 and CD163 antibodies (for M1 and M2, respectively). For both, CD40 and CD163, three populations of cells have been specified: small cells with strong (+++), large cells with weak (+) and cells with no (–) reaction. Due to lack of statistically significant differences between patients with HP, NSIP and IPF, they were classified into a common group and compared to the group of patients with sarcoidosis. The median proportion of macrophage population was as follows: for CD40: 61%, 35%, 2% in patients with SA and 49%, 47%, 3% in patients with other ILD and for CD163: 55%, 35%, 5% in SA and 53%, 43%, 1% in ILD patients, respectively. We found a significantly higher proportion of M1 in SA when compared with other ILD. Our study showed no evidence of defined polarization of alveolar macrophages in different types of interstitial lung diseases. However, we emphasized the role of CD40 positive cells in sarcoidosis and the role of CD163 positive cells in fibrotic diffuse lung diseases. PMID:27536201

  19. Interstitial lung disease in rheumatoid arthritis.

    PubMed

    Ascherman, Dana P

    2010-10-01

    Rheumatoid arthritis (RA) is the most common systemic autoimmune disease in the United States, affecting 1% to 2% of the adult population. Although joints and synovium are the primary targets in this disorder, extra-articular manifestations involving the lungs can lead to significant morbidity and excess mortality. Among the various pulmonary complications that occur in RA, interstitial lung disease (ILD) is the most damaging, with effects ranging from subclinical inflammation/scarring to end-stage pulmonary fibrosis. New insights during the past several years have underscored the epidemiologic impact of clinically/functionally significant RA-associated ILD (RA-ILD) and have begun to identify factors contributing to the pathogenesis of this potentially devastating complication of RA. Despite these advancements, the complexity of RA-ILD and the lack of reliable predictors for disease progression highlight the need for improved biomarker development. Establishing such detailed molecular signatures will ultimately guide the application and timing of therapeutic agents that include immunomodulators as well as newly studied antifibrotic agents.

  20. Genetic testing in diffuse parenchymal lung disease

    PubMed Central

    2012-01-01

    Diffuse parenchymal lung diseases (DPLD) represent a diverse group of disorders affecting the distal lung parenchyma, specifically the tissue and spaces surrounding the alveoli, which may be filled with inflammatory cells, proliferating fibroblasts or established fibrosis, often leading to architectural distortion and impaired gas exchange. While the underlying pathogenetic mechanisms are known or inferred for some DPLD (such as sarcoidosis, silicosis, drug reactions and collagen vascular diseases), the pathogenesis of the majority of these entities - particularly those characterized by progressive fibrosis - is poorly understood. Several lines of evidence indicate that the development of pulmonary fibrosis is genetically determined. They include: 1. familial clustering; 2. the occurrence of pulmonary fibrosis in the context of rare inherited disorders; 3. substantial variability in the development of pulmonary fibrosis amongst individuals exposed to organic or inorganic dusts; 4. difference in susceptibility to fibrogenic stimuli amongst inbred strains of mice. This review focuses on idiopathic pulmonary fibrosis (IPF) and sarcoidosis, the two most common DPLD and the two entities for which there is stronger evidence of a genetic predisposition, although how aberrant genes interact with each other and with environmental factors, such as smoking in IPF and infectious agents in sarcoidosis, in determining disease susceptibility and clinical phenotypes is largely unknown. Finally, we discuss practical issues and implications for both patients and physicians of recent advances in the genetics of sarcoidosis and IPF. PMID:23075428

  1. [CYSTIC FIBROSIS: CARE OF THE LUNG DISEASE].

    PubMed

    Hubert, Dominique

    2015-10-01

    (Rh-DNase) and/or hydration (hypertonic saline) nebulisations, Moreover, treatment with inhaled antibiotics is indicated (tobramycin, colistine or aztreonam lysine) for chronic lung infection with Pseudomonas aeruginosa (PA). The treatment regimen also includes bronchodilators for bronchospasms and azithromycin. Regular physical activity is recommended. A treatment potentiating the CFTR protein, ivacaftor, is now indicated for patients with a class 3 mutation. Initial bronchial infection with PA must be treated as soon as possible in order to eradicate the pathogen. Pulmonary exacerbations require antibiotic courses, either orally or intravenously for PA infection. Complications require hospitalisation, with thoracic chest tube placement for a pneumothorax or bronchial artery embolisation for massive hemoptysis. Oxygen therapy and non-invasive ventilation with a nasal mask become necessary when respiratory insufficiency progresses, justifying the initiation of the lung transplant process. Lung disease affects the prognosis of cystic fibrosis, therefore its management in cystic fibrosis centres is of utmost importance. Maintenance treatment mainly relies on daily chest physiotherapy, which can be facilitated by mucolytic PMID:26749716

  2. [Interstitial lung disease in rheumatoid arthritis].

    PubMed

    Froidevaux-Janin, Sylvie; Dudler, Jean; Nicod, Laurent P; Lazor, Romain

    2011-11-23

    Interstitial lung disease (ILD) is found in up to 30% of patients with rheumatoid arthritis (RA) and is clinically manifest in 5 to 10%, resulting in significant morbidity and mortality. The most frequent histopathological forms are usual interstitial pneumonia and nonspecific interstitial pneumonia. Another recently described presentation is combined pulmonary fibrosis and emphysema. Similarly to idiopathic pulmonary fibrosis, acute exacerbation of ILD may occur in RA and is associated with severe prognosis. Smoking is a known risk factor of RA and may also play a role in the pathogenesis of RA-associated ILD, in combination with genetic and immunologic mechanisms. Several treatments of RA may also lead to drug-induced ILD.

  3. [Hydatid cyst disease mimicking metastatic lung disease: a case report].

    PubMed

    Yiyit, Nurettin; Görür, Rauf; Candaş, Fatih Hikmet; Yıldızhan, Akın; Turhan, Vedat; Işıtmangil, Turgut

    2011-01-01

    Pulmonary hydatid cysts usually present as a single lesion, whereas multiple cases are rare. It is not easy to distinguish hydatid cyst and nodular lesions radiologically. Chest radiograph of a 22 years-old male patient who was admitted due to right sided chest pain, revealed bilateral pulmonary nodules. His computerized tomography (CT) showed 34 nodular densities in the right lung and 21 nodular densities in the left lung. At that time, metastatic lung disease was suggested . Tru-cut lung biopsy was non-diagnostic. Anti-E. granulosus IgG (ELISA) was positive and hydatid cyst disease (HCD) was set as a prediagnosis. A right thoracotomy was performed and more cysts in number than those in tomography were observed intraoperatively. Postoperatively, 800 mg per day albendazole treatment was started. CT at the second month of medical therapy revealed that the lesions were stable in number but their sizes were smaller. CT of the fourth month showed that some of the lesions became cavitary. HCD should be kept in to mind in case of doubtful radiological findings. Although main treatment modality is surgery for HCD, when all cysts can not remove with the surgical treatment in patient with multiple cysts, medical treatment can be administered. PMID:21776601

  4. [Anti-nicotine education applied in relation of parents of the diseased children on chronic allergic diseases of respiratory system].

    PubMed

    Przybylski, Grzegorz; Gołda, Ryszard; Pyskir, Jerzy; Pasińska, Magdalena; Ludwikowski, Grzegorz; Kuziemski, Arkadiusz; Kopiński, Piotr

    2006-01-01

    The allergies of respiratory system are at children the frequent illnesses. Among favorable them factors, risk on passive smoking tobacco can be also. Passive smoking is defined as risk non-smoking on tobacco smoke in environment. Recent reports represent that smoking in home environment tobacco increase on passive smokers' asthma morbidity, especially children in school age. It in it was report the necessity of leadership of anti-nicotine education was underlined in the face of smoking parents. It bets that she should motivate she better parents to cessation smoking, using authority of doctor and love parental. Acting we decided with these principles to analyze effectiveness two year anti-nicotine education which be applied in the face of all treated smoking parents of children with reason of chronic allergic diseases of respiratory system in out-patients. The study comprised parents of 146 children at the Allergy out-Patients clinic, who were diagnosed and cured in years 2003-2005. Generally were 292 persons. The children be treated with reason of bronchial asthma and allergic rhinitis. It the data on subject of smoking of tobacco were collected was on basis of interview got from parents during visits at information bureau on beginning the treatment the children, in his track as well as after two years of education. The anti-nicotine education was applied by whole period of observation during routine medical visits. In moment beginning of treatment in studied group the parents' and education children (n = 292) it 79 the parents' couple did not smoke. Smoking parents among remaining 67 steams were. From among them parents 13 children smoked both, only father in 36 cases smoked and mother in remaining 18 parents' couple smoked. 80 parents smoked with generally. 63 persons after two years of anti-nicotine education the nonsmoking committed one from group smoking. 22 persons among them were from among 24 fathers and 17 mothers' peer in which smoked both parents

  5. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  6. Oral tolerance in neonates: from basics to potential prevention of allergic disease.

    PubMed

    Verhasselt, V

    2010-07-01

    Oral tolerance refers to the observation that prior feeding of an antigen induces local and systemic immune tolerance to that antigen. Physiologically, this process is probably of central importance for preventing inflammatory responses to the numerous dietary and microbial antigens present in the gut. Defective oral tolerance can lead to gut inflammatory disease, food allergies, and celiac disease. In the last two cases, the diseases develop early in life, stressing the necessity of understanding how oral tolerance is set up in neonates. This article reviews the parameters that have been outlined in adult animal models as necessary for tolerance induction and assesses whether these factors operate in neonates. In addition, we highlight the factors that are specific for this period of life and discuss how they could have an impact on oral tolerance. We pay particular attention to maternal influence on early oral tolerance induction through breast-feeding and outline the major parameters that could be modified to optimize tolerance induction in early life and possibly prevent allergic diseases. PMID:20485330

  7. Staphylococcus δ-toxin promotes mouse allergic skin disease by inducing mast cell degranulation

    PubMed Central

    Nakamura, Yuumi; Oscherwitz, Jon; Cease, Kemp B.; Chan, Susana M.; Muñoz-Planillo, Raul; Hasegawa, Mizuho; Villaruz, Amer E.; Cheung, Gordon Y. C.; McGavin, Martin J.; Travers, Jeffrey B.; Otto, Michael; Inohara, Naohiro; Núñez, Gabriel

    2013-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15 to 30% of children and ~5% of adults in industrialized countries1. Although the pathogenesis of AD is not fully understood, the disease is mediated by an abnormal immunoglobulin E (IgE) immune response in the setting of skin barrier dysfunction2. Mast cells (MCs) contribute to IgE-mediated allergic disorders including AD3. Upon activation, MCs release their membrane-bound cytosolic granules leading to the release of multiple molecules that are important in the pathogenesis of AD and host defense4. More than 90% of AD patients are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbor the pathogen5. Several Staphylococcal exotoxins (SEs) can act as superantigens and/or antigens in models of AD6. However, the role of these SEs in disease pathogenesis remains unclear. Here, we report that culture supernatants of S. aureus contain potent MC degranulation activity. Biochemical analysis identified δ-toxin as the MC degranulation-inducing factor produced by S. aureus. MC degranulation induced by δ-toxin depended on phosphoinositide 3-kinase (PI3K) and calcium (Ca2+) influx, but unlike that mediated by IgE crosslinking, it did not require the spleen tyrosine kinase (Syk). In addition, IgE enhanced δ-toxin-induced MC degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from AD patients produced high levels of δ-toxin. Importantly, skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted IgE and IL-4 production, as well as inflammatory skin disease. Furthermore, enhancement of IgE production and dermatitis by δ-toxin was abrogated in KitW-sh/W-sh MC-deficient mice and restored by MC reconstitution. These studies identify δ-toxin as a potent inducer of MC degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease. PMID:24172897

  8. Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine.

    PubMed

    Agache, Ioana; Akdis, Cezmi A

    2016-07-01

    Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management.

  9. General anesthesia exposure in early life reduces the risk of allergic diseases: A nationwide population-based cohort study.

    PubMed

    Kuo, Ho-Chang; Yang, Ya-Ling; Ho, Shu-Chen; Guo, Mindy Ming-Huey; Jiang, Jyun-Hong; Huang, Ying-Hsien

    2016-07-01

    General anesthesia (GA) has been used for second line treatment strategy for status asthmaticus in pediatric patients. The association between GA in children and risk of followed-up allergic diseases is unclear. This study aims to assess the risk of allergic diseases after GA in children.We did a nationwide retrospective cohort study by analyzing data from the National Health Insurance Research Database (NHIRD) in Taiwan. The subsequent risks for allergic diseases, including asthma (ICD-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between exposure to GA and none before 1 year of age throughout the follow-up period using the Cox proportional hazards model.Insurance claims data for 32,742 children younger than 1 year old from all insured children in the NHIRD. Of those, 2358 subjects were exposed to GA; 414 and 1944 children exposed to mask and intubation ventilation, respectively, served as the study cohort, whereas the remaining 30,384 children made up the comparison cohort. Children in the GA group were at a lower risk of developing asthma, AR and AD, with adjusted hazard ratios of 0.67 (0.62-0.72, 95%CI), 0.72 (0.68-0.77, 95%CI), 0.60 (0.56-0.64, 95%CI), respectively.Children who were exposed to GA in early life before 1 year of age had reduced risk of subsequently developing allergic diseases such as asthma, AD, and AR, when compared with general population. PMID:27428241

  10. Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

    PubMed

    Dharajiya, Nilesh; Vaidya, Swapnil; Sinha, Mala; Luxon, Bruce; Boldogh, Istvan; Sur, Sanjiv

    2009-01-01

    According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE) using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1), Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1) Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2) Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation. PMID:20027288

  11. Respiratory Allergic Disorders.

    PubMed

    Woloski, Jason Raymond; Heston, Skye; Escobedo Calderon, Sheyla Pamela

    2016-09-01

    Allergic asthma refers to a chronic reversible bronchoconstriction influenced by an allergic trigger, leading to symptoms of cough, wheezing, shortness of breath, and chest tightness. Allergic bronchopulmonary aspergillosis is a complex hypersensitivity reaction, often in patients with asthma or cystic fibrosis, occurring when bronchi become colonized by Aspergillus species. The clinical picture is dominated by asthma complicated by recurrent episodes of bronchial obstruction, fever, malaise, mucus production, and peripheral blood eosinophilia. Hypersensitivity pneumonitis is a syndrome associated with lung inflammation from the inhalation of airborne antigens, such as molds and dust. PMID:27545731

  12. Stem Cells and Regenerative Medicine in Lung Biology and Diseases

    PubMed Central

    Lau, Allison N; Goodwin, Meagan; Kim, Carla F; Weiss, Daniel J

    2012-01-01

    A number of novel approaches for repair and regeneration of injured lung have developed over the past several years. These include a better understanding of endogenous stem and progenitor cells in the lung that can function in reparative capacity as well as extensive exploration of the potential efficacy of administering exogenous stem or progenitor cells to function in lung repair. Recent advances in ex vivo lung engineering have also been increasingly applied to the lung. The current status of these approaches as well as initial clinical trials of cell therapies for lung diseases are reviewed below. PMID:22395528

  13. Allergic rhinoconjunctivitis in the Australian population: Burden of disease and attitudes to intranasal corticosteroid treatment

    PubMed Central

    Sacks, Raymond; Theron, Paul N.

    2013-01-01

    Background: Allergic rhinoconjunctivitis (AR/C) is a global health problem causing significant morbidity and has a major impact on quality of life (QOL) and health expenditure. Despite the widespread prevalence, the overall health impact of AR/C may be underappreciated. The results of a survey designed to capture the burden of allergic rhinitis within the Asia-Pacific region have been published recently. Of particular note when evaluating treatment in this region was the fact that despite the value of intranasal corticosteroid (INCS) use, only a small percentage of patients used them. Whether this same trend is present within the population of Australian sufferers is unknown. This study examines the burden of AR/C and explores use of, and attitudes, to INCS sprays in the Australian population. Methods: Three hundred three completed interviews from adults and children who had physician-diagnosed AR/C and who were symptomatic or had received treatment in the previous 12 months were analyzed for QOL measures and attitudes to INCS use. Results: Most patients surveyed had received their diagnosis from a general practitioner (GP), and in most cases, a GP provided the majority of ongoing medical care. Only 8% of respondents had consulted a relevant specialist. Diagnostic tests had not been performed in 55% of respondents. The major symptoms causing most distress were nasal congestion and ocular symptoms. The burden of AR/C was considerable; 42% described significant work or school interference because of symptoms, one-third reporting moderate-to-extreme interference with sleep. Despite the significant impact on QOL reported by this sample, 17% had never used INCS and 27% had not used them in the previous 12 months. Respondents' knowledge about INCSs was poor. Conclusion: AR/C is a common disease associated with significant morbidity and impairment of QOL. Improvement in diagnosis, management, and patient education is needed. PMID:24274227

  14. Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease*

    PubMed Central

    Pereira, Daniel Antunes Silva; Kawassaki, Alexandre de Melo; Baldi, Bruno Guedes

    2013-01-01

    The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease. PMID:24473767

  15. Macrophage Chitinase 1 Stratifies Chronic Obstructive Lung Disease

    PubMed Central

    Agapov, Eugene; Battaile, John T.; Tidwell, Rose; Hachem, Ramsey; Patterson, G. Alexander; Pierce, Richard A.; Atkinson, Jeffrey J.; Holtzman, Michael J.

    2009-01-01

    Diagnosis and therapy of chronic inflammatory lung disease is limited by the need for individualized biomarkers that provide insight into pathogenesis. Herein we show that mouse models of chronic obstructive lung disease exhibit an increase in lung chitinase production but cannot predict which chitinase family member may be equivalently increased in humans with corresponding lung disease. Moreover, we demonstrate that lung macrophage production of chitinase 1 is selectively increased in a subset of subjects with severe chronic obstructive pulmonary disease, and this increase is reflected in plasma levels. The findings provide a means to noninvasively track alternatively activated macrophages in chronic lung disease and thereby better differentiate molecular phenotypes in heterogeneous patient populations. PMID:19491341

  16. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2013-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2012. Studies support an increase in peanut allergy prevalence in children and exposure to the antibacterial agent triclosan and having filaggrin (FLG) loss-of-function mutations as risk factors for food sensitization. The role of specific foods in causing eosinophilic esophagitis is elucidated by several studies, and microRNA analysis is identified as a possible noninvasive disease biomarker. Studies on food allergy diagnosis emphasize the utility of component testing and the possibility of improved diagnosis through stepped approaches, epitope-binding analysis, and bioinformatics. Treatment studies of food allergy show promise for oral immunotherapy, but tolerance induction remains elusive, and additional therapies are under study. Studies on anaphylaxis suggest an important role for platelet-activating factor and its relationship to the need for prompt treatment with epinephrine. Insights on the pathophysiology and diagnosis of non-IgE-mediated drug allergy are offered, with novel data regarding the interaction of drugs with HLA molecules. Numerous studies support influenza vaccination of persons with egg allergy using modest precautions. Evidence continues to mount that there is cross-talk between skin barrier defects and immune responses in patients with atopic dermatitis. Augmentation of the skin barrier with reduction in skin inflammatory responses will likely lead to the most effective intervention in patients with this common skin disease.

  17. Occupational allergic respiratory diseases in garbage workers: relevance of molds and actinomycetes.

    PubMed

    Hagemeyer, O; Bünger, J; van Kampen, V; Raulf-Heimsoth, M; Drath, C; Merget, R; Brüning, Th; Broding, H C

    2013-01-01

    Exposures to molds and bacteria (especially actinomycetes) at workplaces are common in garbage workers, but allergic respiratory diseases due to these microorganisms have been described rarely. The aim of our study was a detailed analysis of mold or bacteria-associated occupational respiratory diseases in garbage workers. From 2002 to 2011 four cases of occupational respiratory diseases related to garbage handling were identified in our institute (IPA). Hypersensitivity pneumonitis (HP) was diagnosed in three subjects (cases 1-3, one smoker, two non-smokers), occupational asthma (OA) was diagnosed in one subject (case 4, smoker), but could not be excluded completely in case 2. Cases 1 and 2 worked in composting sites, while cases 3 and 4 worked in packaging recycling plants. Exposure periods were 2-4 years. Molds and actinomycetes were identified as allergens in all cases. Specific IgE antibodies to Aspergillus fumigatus were detected exclusively in case 4. Diagnoses of HP were essentially based on symptoms and the detection of specific IgG serum antibodies to molds and actinomycetes. OA was confirmed by bronchial provocation test with Aspergillus fumigatus in case 4. In conclusion, occupational HP and OA due to molds occur rarely in garbage workers. Technical prevention measures are insufficient and the diagnosis of HP is often inconclusive. Therefore, it is recommended to implement the full repertoire of diagnostic tools including bronchoalveolar lavage and high resolution computed tomography in the baseline examination.

  18. Occupational allergic respiratory diseases in garbage workers: relevance of molds and actinomycetes.

    PubMed

    Hagemeyer, O; Bünger, J; van Kampen, V; Raulf-Heimsoth, M; Drath, C; Merget, R; Brüning, Th; Broding, H C

    2013-01-01

    Exposures to molds and bacteria (especially actinomycetes) at workplaces are common in garbage workers, but allergic respiratory diseases due to these microorganisms have been described rarely. The aim of our study was a detailed analysis of mold or bacteria-associated occupational respiratory diseases in garbage workers. From 2002 to 2011 four cases of occupational respiratory diseases related to garbage handling were identified in our institute (IPA). Hypersensitivity pneumonitis (HP) was diagnosed in three subjects (cases 1-3, one smoker, two non-smokers), occupational asthma (OA) was diagnosed in one subject (case 4, smoker), but could not be excluded completely in case 2. Cases 1 and 2 worked in composting sites, while cases 3 and 4 worked in packaging recycling plants. Exposure periods were 2-4 years. Molds and actinomycetes were identified as allergens in all cases. Specific IgE antibodies to Aspergillus fumigatus were detected exclusively in case 4. Diagnoses of HP were essentially based on symptoms and the detection of specific IgG serum antibodies to molds and actinomycetes. OA was confirmed by bronchial provocation test with Aspergillus fumigatus in case 4. In conclusion, occupational HP and OA due to molds occur rarely in garbage workers. Technical prevention measures are insufficient and the diagnosis of HP is often inconclusive. Therefore, it is recommended to implement the full repertoire of diagnostic tools including bronchoalveolar lavage and high resolution computed tomography in the baseline examination. PMID:23835992

  19. Early life exposure to antibiotics and the risk of childhood allergic diseases: an update from the perspective of the hygiene hypothesis.

    PubMed

    Kuo, Chang-Hung; Kuo, Hsuan-Fu; Huang, Ching-Hua; Yang, San-Nan; Lee, Min-Sheng; Hung, Chih-Hsing

    2013-10-01

    The prevalence of allergic diseases has been growing rapidly in industrial countries during recent decades. It is postulated that growing up with less microbial exposure may render the immune system susceptible to a T helper type 2 (Th2)-predominant allergic response-also known as the hygiene hypothesis. This review delineates recent epidemiological and experimental evidence for the hygiene hypothesis, and integrates this hypothesis into the association between early life exposure to antibiotics and the development of allergic diseases and asthma. Several retrospective or prospective epidemiological studies reveal that early exposure to antibiotics may be positively associated with the development of allergic diseases and asthma. However, the conclusion is inconsistent. Experimental studies show that antibiotics may induce the Th2-skewed response by suppressing the T helper type 1 (Th1) response through inhibition of Th1 cytokines and disruption of the natural course of infection, or by disturbing the microflora of the gastrointestinal (GI) tract and therefore jeopardizing the establishment of oral tolerance and regulatory T cell immune responses. The hygiene hypothesis may not be the only explanation for the rapid increase in the prevalence of allergic diseases and asthma. Further epidemiological and experimental studies addressing the issue of the impact of environmental factors on the development of allergic diseases and the underlying mechanisms may unveil novel strategies for the prevention and treatment of allergic diseases in the future.

  20. Respiratory and allergic diseases: from upper respiratory tract infections to asthma.

    PubMed

    Jaber, Raja

    2002-06-01

    Andrographis shortens the duration of the common cold. The one study on Elderberry's use for the flu was encouraging, and the data on the homeopathic remedy Oscillococcinum interesting, but more studies should be performed. Saline washes may be helpful to patients with allergic rhinitis and chronic sinusitis. Patients also may try the German combination (available in the United States) of elderberry, vervain, gentian, primrose, and sorrel that has been tested in randomized clinical trials. Bromelain is safe to try; the trials of bromelain supplementation were promising but were never repeated. The preceding suggestions need to be grounded in a program based on optimal medical management. Patients need to be well educated in the proper medical management of their disease and skilled at monitoring disease stability and progress. Asthmatic patients need to monitor their bronchodilator usage and peak flow meter measurements to step up their medical treatment in a timely manner, if needed. Patients welcome physician guidance when exploring the breadth of treatments available today. A true patient-physician partnership is always empowering to patients who are serious about regaining their function and health.

  1. The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease.

    PubMed

    O'Dwyer, David N; Dickson, Robert P; Moore, Bethany B

    2016-06-15

    The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID:27260767

  2. TGF-β: An Important Mediator of Allergic Disease and a Molecule with Dual Activity in Cancer Development

    PubMed Central

    Tirado-Rodriguez, Belen; Segura-Medina, Patricia; Huerta-Yepez, Sara

    2014-01-01

    The transforming growth factor-β (TGF-β) superfamily is a family of structurally related proteins that includes TGF-β, activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF-β superfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF-β is involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF-β receptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF-β with various pathological entities such as allergic diseases and cancer, yielding a new area of research known as “allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF-β is involved. Here, we review recent studies that suggest an important role for TGF-β in both allergic disease and cancer progression. PMID:25110717

  3. Respiratory failure due to infliximab induced interstitial lung disease.

    PubMed

    Kakavas, Sotiris; Balis, Evangelos; Lazarou, Vasiliki; Kouvela, Marousa; Tatsis, Georgios

    2013-01-01

    Although poorly understood, interstitial lung disease has been reported as a possible complication of tumor necrosis factor alpha inhibitors. We report a case of interstitial lung disease in a 64-year-old man with psoriasis 3 weeks after the initiation of infliximab treatment. The patient had received two fortnightly infusions of infliximab following a short course of methotrexate. Thoracic computed tomography showed bilateral ground glass and interstitial infiltrates, while the results of microbiology and immunologic workup were negative. Likewise, bronchoalveolar lavage detected neither typical nor atypical pathogens. Infliximab-induced interstitial lung injury was suspected and corticosteroid therapy was administered which resulted in rapid clinical and radiological improvement. This is one of the few reported cases of interstitial lung disease due to infliximab in the psoriasis population. The patient had no pre-existing lung pathology, while his previous exposure to methotrexate was minimal and was not temporally associated with the induction of interstitial lung disease.

  4. Common lung conditions: chronic obstructive pulmonary disease.

    PubMed

    Delzell, John E

    2013-06-01

    The etiology of chronic obstructive pulmonary disease (COPD) is chronic lung inflammation. In the United States, this inflammation most commonly is caused by smoking. COPD is diagnosed when an at-risk patient presents with respiratory symptoms and has irreversible airway obstruction indicated by a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.7. Management goals for COPD include smoking cessation, symptom reduction, exacerbation reduction, hospitalization avoidance, and improvement of quality of life. Stable patients with COPD who remain symptomatic despite using short-acting bronchodilators should start inhaled maintenance drugs to reduce symptoms and exacerbations, avoid hospitalizations, and improve quality of life. A long-acting anticholinergic or a long-acting beta2-agonist (LABA) can be used for initial therapy; these drugs have fewer adverse effects than inhaled corticosteroids (ICS). If patients remain symptomatic despite monotherapy, dual therapy with a long-acting anticholinergic and a LABA, or a LABA and an ICS, may be beneficial. Triple therapy (ie, a long-acting anticholinergic, a LABA, and an ICS) also is used, but it is unclear if triple therapy is superior to dual therapy. Roflumilast, an oral selective inhibitor of phosphodiesterase 4, is used to manage moderate to severe COPD. Continuous oxygen therapy is indicated for patients with COPD who have severe hypoxemia (ie, PaO2 less than 55 mm Hg or an oxygen saturation less than 88% on room air). Nonpharmacologic strategies also are useful to improve patient outcomes. Pulmonary rehabilitation improves dyspnea and quality of life. Pulmonary rehabilitation after an acute exacerbation reduces hospitalizations and mortality, and improves quality of life and exercise capacity. Smoking cessation is the most effective management strategy for reducing morbidity and mortality in patients with COPD. Lung volume reduction surgery, bullectomy, and lung transplantation are

  5. [Radiation diagnosis of diffuse lung diseases: Part I].

    PubMed

    Stashuk, G A; Dubrova, S E

    2005-01-01

    Based on the data on 150 patients with diffuse lung diseases, the authors present the X-ray and computed topographic semiotics of changes in lung tissue in a number of diseases from this group. The differential diagnosis of diffuse lung diseases has certain difficulties whose solution is association with the application of complex radiation studies (digital fluorography, classical X-ray study, X-ray computed tomography, and magnetic resonance imaging). These techniques not only assess the status of the parenchyma of the lung and the extent of a process, but also permit a follow-up monitoring and evaluation of the efficiency of the therapy performed.

  6. Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development.

    PubMed

    Harwanegg, Christian; Hiller, Reinhard

    2005-01-01

    In the emerging field of Functional Proteomics, protein microarrays are considered to be one of the most promising tools for the simultaneous analysis of the a) abundance, b) function, and c) interaction of proteins on a system-wide scale. Resting on the technological grounds of widely used DNA biochips, the great power of microarray-based miniature solid-phase immunoassays lies in their potential to investigate in parallel large numbers of analyte pairs in a variety of biological samples. Consequently, this has fueled aspirations that protein microarrays may serve as tools for the high-throughput functional investigation of complete proteomes and, moreover, that they will develop into promising candidates for innovative in-vitro diagnostic (IVD) applications. To date, published examples of protein microarrays for IVD purposes have included tests for allergy, autoimmune and infectious diseases. Here, we discuss recent advancements in the development of protein microarrays for the profiling of IgE antibodies in the diagnosis of Type 1-related allergic diseases.

  7. Changing anaerobic spectrum in suppurative lung disease: a case report.

    PubMed

    Beena, V K; Kumari, G R; Rao, P V; Murty, M V; Shivananda, P G

    1996-01-01

    A spectrum of three different anaerobes were isolated from a debilitated patient with suppurative lung disease, within a two-year period. Repeated isolation from three consecutive samples and symptomatic relief with metronidazole provide clinical evidence of anaerobic lung infection. This case emphasizes the importance of anaerobic culture in cases of protracted pulmonary suppurative disease. PMID:8822645

  8. Intravascular laser therapy in different forms of lung diseases

    NASA Astrophysics Data System (ADS)

    Kirillov, M. N.; Reshetnikov, V. A.; Kazhekin, O. A.; Shepelenko, A. F.

    1993-06-01

    The potentions of laser intravascular therapy in elimination of pyogenic and inflammatory intoxication in cases of acute pneumonia, pyo-destructive diseases (including posttraumatic diseases) of the lungs are studied clinically.

  9. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. PMID:26135330

  10. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.

  11. Chronic suppurative lung disease in adults

    PubMed Central

    Mangardich, Antranik

    2016-01-01

    Chronic suppurative lung disease (CSLD), characterized by a bronchiectasis-like syndrome in the absence of bronchial dilatation, is well described in the pediatric literature. In some patients, it may be a precursor of bronchiectasis. In adults, this syndrome has not been well described. We present four adult patients without obvious causative exposures who presented with prolonged cough and purulent sputum. Sputum cultures revealed a variety of Gram negative bacteria, fungi and mycobacteria. High resolution CT scanning did not reveal bronchiectasis. Evaluation revealed underlying causes including immunodeficiency in two, and Mycobacterium avium infection. One patient subsequently developed bronchiectasis. All patients improved with therapy. CSLD occurs in adults and has characteristics that distinguish it from typical chronic bronchitis. These include the lack of causative environmental exposures and infection with unusual pathogens. Evaluation and treatment of these patients similar to bronchiectasis patients may lead to clinical improvement. PMID:27747039

  12. Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model.

    PubMed

    de Haar, Colin; Hassing, Ine; Bol, Marianne; Bleumink, Rob; Pieters, Raymond

    2005-10-01

    To gain more insight into the mechanisms of particulate matter (PM)-induced adjuvant activity, we studied the kinetics of airway toxicity/inflammation and allergic sensitization to ovalbumin (OVA) in response to ultrafine carbon black particles (CBP). Mice were exposed intranasally to OVA alone or in combination with different concentrations of CBP. Airway toxicity and inflammation were assessed at days 4 and 8. Immune adjuvant effects were studied in the lung draining peribronchial lymph nodes (PBLN) at day 8. Antigen-specific IgE was measured at days 21 and 28, whereas allergic airway inflammation was studied after OVA challenges (day 28). Results show that a total dose of 200 microg CBP per mouse, but not 20 microg or 2 microg, induced immediate airway inflammation. This 200 microg CBP was the only dose that had immune adjuvant activity, by inducing enlargement of the PBLN and increasing OVA-specific production of Th2 cytokines (IL-4, IL-5, and IL-10). The immune adjuvant activity of 200 microg CBP dosing was further examined. Whereas increased OVA-specific IgE levels in serum on day 21 confirms systemic sensitization, this was further supported by allergic airway inflammation after challenges with OVA. Our data show a link between early airway toxicity and adjuvant effects of CBP. In addition, results indicate that local cytokine production early after exposure to CBP is predictive of allergic airway inflammation. In addition this model appears suitable for studying the role of airway toxicity, inflammation and other mechanisms of particle adjuvant activity, and predicting the adjuvant potential of different particles.

  13. Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene

    PubMed Central

    Bloomfield, Sally F; Rook, Graham AW; Scott, Elizabeth A; Shanahan, Fergus; Stanwell-Smith, Rosalind; Turner, Paul

    2016-01-01

    Aims: To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease. Methods: Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim. Results: Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe–host interactions, the term ‘hygiene hypothesis’ is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures. Conclusion: Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term ‘hygiene hypothesis’ must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about

  14. [Non-allergic gluten sensitivity. A controversial disease - or not yet sufficiently explored?].

    PubMed

    Raithel, Martin; Kluger, Anna Katharina; Dietz, Birgit; Hetterich, Urban

    2016-07-01

    The avoidance of wheat, gluten and other cereal products is a growing phenomenon in industrialized countries. The diagnostic criteria of celiac disease and of food allergy to wheat flour and/or other cereals are clearly defined. Only about 0.5-25 % of the population are affected from both of these immunological diseases.Nevertheless, there exists a significantly greater proportion of people reporting at least subjectively significant complaints and quality of life improvements after switching to a wheat- or gluten-free diet. Celiac disease or wheat allergy cannot be detected in these individuals on the basis of established criteria. The absence of clear diagnostic autoimmune or allergic criteria in these wheat sensitive patients has resulted in the description of non-celiac gluten sensitivity.It is clinically detectable in only very few individuals and may manifest with either intestinal, extra-intestinal or neurovegetative and psychosomatic symptoms, respectively. However, non-celiac disease gluten sensitivity has to be differentiated critically from irritable bowel syndrome, carbohydrate malassimilation, postinfectious conditions and psychosomatic diseases.Pathophysiologically, non-celiac disease gluten sensitivity is still poorly characterized; several non-immunological mechanisms are discussed to contribute to non-celiac gluten sensitivity. These include the effects of fructo- and galacto-oligosaccharides, of trypsin inhibitors of amylase, and wheat lectin agglutinins, which may influence or modulate intestinal permeability and/or a non-specific immune or effector cell degranulation within the gastrointestinal tract. In addition, further metabolic effects with direct or indirect influence on the intestinal flora are currently discussed.In addition to subjectively reported changes in symptoms that may affect variably intestinal, as well as extra-intestinal and/or neuropsychiatric symptoms, some studies suggest that there is little reproducibility of

  15. [Non-allergic gluten sensitivity. A controversial disease - or not yet sufficiently explored?].

    PubMed

    Raithel, Martin; Kluger, Anna Katharina; Dietz, Birgit; Hetterich, Urban

    2016-07-01

    The avoidance of wheat, gluten and other cereal products is a growing phenomenon in industrialized countries. The diagnostic criteria of celiac disease and of food allergy to wheat flour and/or other cereals are clearly defined. Only about 0.5-25 % of the population are affected from both of these immunological diseases.Nevertheless, there exists a significantly greater proportion of people reporting at least subjectively significant complaints and quality of life improvements after switching to a wheat- or gluten-free diet. Celiac disease or wheat allergy cannot be detected in these individuals on the basis of established criteria. The absence of clear diagnostic autoimmune or allergic criteria in these wheat sensitive patients has resulted in the description of non-celiac gluten sensitivity.It is clinically detectable in only very few individuals and may manifest with either intestinal, extra-intestinal or neurovegetative and psychosomatic symptoms, respectively. However, non-celiac disease gluten sensitivity has to be differentiated critically from irritable bowel syndrome, carbohydrate malassimilation, postinfectious conditions and psychosomatic diseases.Pathophysiologically, non-celiac disease gluten sensitivity is still poorly characterized; several non-immunological mechanisms are discussed to contribute to non-celiac gluten sensitivity. These include the effects of fructo- and galacto-oligosaccharides, of trypsin inhibitors of amylase, and wheat lectin agglutinins, which may influence or modulate intestinal permeability and/or a non-specific immune or effector cell degranulation within the gastrointestinal tract. In addition, further metabolic effects with direct or indirect influence on the intestinal flora are currently discussed.In addition to subjectively reported changes in symptoms that may affect variably intestinal, as well as extra-intestinal and/or neuropsychiatric symptoms, some studies suggest that there is little reproducibility of

  16. The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases.

    PubMed

    Sayan, Mutlay; Mossman, Brooke T

    2016-01-01

    The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres. Most notably, inflammasome activation appears to regulate the balance between tissue repair and inflammation after inhalation of pathogenic pollutants such as asbestos, crystalline silica (CS), and airborne particulate matter (PM). Different types of fibres and particles may have distinct mechanisms of inflammasome interaction and outcome. This review summarizes the structure and function of inflammasomes, the interplay between various chemokines and cytokines and cell types of the lung and pleura after inflammasome activation, and the events leading to the development of non-malignant (allergic airway disease and chronic obstructive pulmonary disease (COPD), asbestosis, silicosis) and malignant (mesothelioma, lung cancer) diseases by pathogenic particulates. In addition, it emphasizes the importance of communication between cells of the immune system, target cells of these diseases, and components of the extracellular matrix (ECM) in regulation of inflammasome-mediated events. PMID:27650313

  17. IgE in the diagnosis and treatment of allergic disease.

    PubMed

    Platts-Mills, Thomas A E; Schuyler, Alexander J; Erwin, Elizabeth A; Commins, Scott P; Woodfolk, Judith A

    2016-06-01

    Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the "allergic" disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow's milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response. PMID:27264001

  18. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect stings.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2004-07-01

    This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect venom that were reported primarily in the Journal of Allergy and Clinical Immunology from 2002 through 2003. Among the topics highlighted are new insights into the pathogenesis of atopic dermatitis and potential strategies for more effective treatment of the atopic march. Patients should remain supine with raised legs during anaphylactic shock because upper body elevation could result in sudden death from loss of venous return to the heart. A major advance in food allergy was that humanized, monoclonal anti-IgE antibody showed protection against peanut-induced anaphylaxis. In addition to studies elucidating mechanisms of drug hypersensitivity, a clinical study showed patients with a history of prior penicillin allergy with negative penicillin allergy test results are unlikely to experience reactions or resensitization on subsequent oral courses of penicillin. Lastly, there are new recommendations for patients with convincing insect sting reaction histories but negative skin test responses to venom.

  19. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2014-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2013. Studies on food allergy suggest that (1) 7.6% of the US population is affected, (2) a "healthy" early diet might prevent food allergy, (3) the skin might be an important route of sensitization, (4) allergen component testing might aid diagnosis, (5) the prognosis of milk allergy might be predictable through early testing, (6) oral or sublingual immunotherapy show promise but also have caveats, and (7) preclinical studies show promising alternative modes of immunotherapy and desensitization. Studies on eosinophilic esophagitis show a relationship to connective tissue disorders and that dietary management is an effective treatment for adults. Markers of anaphylaxis severity have been determined and might inform potential diagnostics and therapeutic targets. Insights on serum tests for drug and insect sting allergy might result in improved diagnostics. Genetic and immune-mediated defects in skin epithelial differentiation contribute to the severity of atopic dermatitis. Novel management approaches to treatment of chronic urticaria, including use of omalizumab, are being identified.

  20. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2010.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2011-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year.

  1. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2015-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. Diagnostic tests are improving, with early studies suggesting the possibility of developing novel cellular tests with increased diagnostic utility. Treatment trials continue to show the promise and limitations of oral immunotherapy, and mechanistic studies are elucidating pathways that might define the degree of efficacy of this treatment. Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD.

  2. The contribution of biotechnology toward progress in diagnosis, management, and treatment of allergic diseases.

    PubMed

    Palomares, O; Crameri, R; Rhyner, C

    2014-12-01

    'Biotechnology' has been intuitively used by humans since thousands of years for the production of foods, beverages, and drugs based on the experience without any scientific background. However, the golden era of this discipline emerged only during the second half of the last century. Incredible progresses have been achieved on all fields starting from the industrialization of the production of foods to the discovery of antibiotics, the decipherment of the genetic code, and rational approaches to understand and define the status we now call 'healthy'. The extremely complex interactions between genetic background, life style, and environmental factors influencing our continuously increasing life span have become more and more evident and steadily generate new questions which are only partly answered. Here, we try to summarize the contribution of biotechnology to our understanding, control, and cure of IgE-mediated allergic diseases. We are aware that a review of such a vast topic can never cover all aspects of the progress achieved in the different fields.

  3. The effects of pregnancy on the exacerbation and development of maternal allergic respiratory disease.

    PubMed

    Pucheu-Haston, Cherie M; Copeland, Lisa B; Haykal-Coates, Najwa; Ward, Marsha D W

    2009-12-01

    The T-helper 2 (T(H)2) bias associated with pregnancy may predispose the pregnant mother to the development or exacerbation of allergic disease. To determine the effects of pregnancy on pre-existing maternal sensitization, we sensitized BALB/c mice before breeding by two intratracheal aspiration (IA) exposures to the fungal allergen, Metarhizium anisopliae crude antigen (MACA). Some mice also received three IA exposures to MACA on gestational days 11, 15, and 19. After weaning, all mice were challenged IA with MACA before killing. To determine the effects of pregnancy on susceptibility to future sensitization, naïve parous and nulliparous BALB/c mice were sensitized by three IA exposures to MACA or to Hank's buffered salt solution vehicle control. Pregnancy did not have a significant effect on individual inflammatory parameters (airway responsiveness to methacholine, total serum and bronchoalveolar lavage fluid (BALF) IgE, BALF total protein, lactate dehydrogenase activity, and total and differential cell counts) following allergen challenge in sensitized mice, regardless of post-breeding allergen exposure. In conclusion there was a weak inhibition of the overall response in mice exposed to allergen during pregnancy compared to identically treated nulliparous mice. In contrast, parous mice that did not encounter allergen post-breeding tended to have exacerbated responses. Parity had no significant impact on future susceptibility to sensitization. PMID:19845451

  4. Dietary n-3 LC-PUFA during the perinatal period as a strategy to minimize childhood allergic disease.

    PubMed

    Makrides, Maria; Gunaratne, Anoja W; Collins, Carmel T

    2013-01-01

    There has been growing interest in the role of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in the modulation of the immune response during early childhood and whether this may translate to a reduction in childhood allergic disease. Several randomized controlled trials of n-3 LC-PUFA supplementation have been reported, largely involving children who are at high hereditary risk of developing allergies. These studies relatively consistently indicate that supplementation during pregnancy results in fewer children with atopic eczema in early childhood. On the other hand, supplementation studies confined exclusively to the postnatal period have demonstrated mixed results with one trial showing no effect and the other suggesting a transient effect on symptoms of respiratory disease. In summary, supplementation with n-3 LC-PUFA during the perinatal period and before allergic response is established may be a useful strategy to prevent early childhood allergic disease in children at high hereditary risk. Further work is needed to establish the optimal period of supplementation and whether longer term benefits exist. PMID:24107505

  5. Dietary n-3 LC-PUFA during the perinatal period as a strategy to minimize childhood allergic disease.

    PubMed

    Makrides, Maria; Gunaratne, Anoja W; Collins, Carmel T

    2013-01-01

    There has been growing interest in the role of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in the modulation of the immune response during early childhood and whether this may translate to a reduction in childhood allergic disease. Several randomized controlled trials of n-3 LC-PUFA supplementation have been reported, largely involving children who are at high hereditary risk of developing allergies. These studies relatively consistently indicate that supplementation during pregnancy results in fewer children with atopic eczema in early childhood. On the other hand, supplementation studies confined exclusively to the postnatal period have demonstrated mixed results with one trial showing no effect and the other suggesting a transient effect on symptoms of respiratory disease. In summary, supplementation with n-3 LC-PUFA during the perinatal period and before allergic response is established may be a useful strategy to prevent early childhood allergic disease in children at high hereditary risk. Further work is needed to establish the optimal period of supplementation and whether longer term benefits exist.

  6. Association of allergic sensitization with infectious diseases burden in Roma and non-Roma children.

    PubMed

    Michos, Athanasios; Terzidis, Agis; Kanariou, Maria; Kalampoki, Vasiliki; Koilia, Christina; Giannaki, Maria; Liatsis, Manolis; Pangalis, Anastasia; Petridou, Eleni

    2011-03-01

    The hypothesis whether exposure to certain infections protects from atopy remains equivocal. To further investigate this, we compared serologic markers of infection and allergic sensitization prevalence in Roma children, who live under unfavorable hygienic conditions that facilitate the spread of infections, and non-Roma children who live in the same area. Analyses included 98 Roma and 118 non-Roma children. Serum IgG antibodies for 13 foodborne- airborne- and bloodborne infectious agents were determined, and a cumulative index of exposure was calculated by adding one point for each positive infection. Specific serum IgE to certain common food- and aero-allergens was also tested. and positivity to any of them was defined as indication of atopy. Roma children were found significantly more seropositive for T. gondii, Hepatitis A, H. pylori, HSV-1, CMV, and Hepatitis B (p < 0.0001). Non-Roma children were found more seropositive for RSV and M. pneumonia (p < 0.0001). Regarding the overall prevalence of atopy or the specific IgE responses to the allergens tested, no statistically significant differences were found between Roma and non-Roma children. A positive association of the cumulative index of exposure to infections with atopy was found in the non-Roma children (OR: 1.38, 95% CI: 1.08-1.75, p = 0.01) and in the total population (OR: 1.42, 95% CI: 1.11-1.83, p = 0.01). Regarding the specific infectious agents tested, a statistically significant positive association of atopy with seropositivity was found for M. pneumoniae in the non-Roma children (OR: 3.93, 95% CI: 1.39) as well as in the total population studied (OR: 2.83, 95% CI: 1.32-6.07, p = 0.01). Despite the higher burden of exposure to the battery of the infectious agents tested among Roma children, no protective effect for allergic disease development was evident. On the contrary, a positive association of exposure to infections with evidence of atopy was found, especially evident in the non-Roma children.

  7. Ligation of TLR7 on CD19(+) CD1d(hi) B cells suppresses allergic lung inflammation via regulatory T cells.

    PubMed

    Khan, Adnan R; Amu, Sylvie; Saunders, Sean P; Hams, Emily; Blackshields, Gordon; Leonard, Martin O; Weaver, Casey T; Sparwasser, Tim; Sheils, Orla; Fallon, Padraic G

    2015-06-01

    B cells have been described as having the capacity to regulate cellular immune responses and suppress inflammatory processes. One such regulatory B-cell population is defined as IL-10-producing CD19(+) CD1d(hi) cells. Previous work has identified an expansion of these cells in mice infected with the helminth, Schistosoma mansoni. Here, microarray analysis of CD19(+) CD1d(hi) B cells from mice infected with S. mansoni demonstrated significantly increased Tlr7 expression, while CD19(+) CD1d(hi) B cells from uninfected mice also demonstrated elevated Tlr7 expression. Using IL-10 reporter, Il10(-/-) and Tlr7(-/-) mice, we formally demonstrate that TLR7 ligation of CD19(+) CD1d(hi) B cells increases their capacity to produce IL-10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7-elicited CD19(+) CD1d(hi) B cells reduced airway inflammation and associated airway hyperresponsiveness. Using DEREG mice to deplete FoxP3(+) T regulatory cells in allergen-sensitized mice, we show that that TLR7-elicited CD19(+) CD1d(hi) B cells suppress airway hyperresponsiveness via a T regulatory cell dependent mechanism. These studies identify that TLR7 stimulation leads to the expansion of IL-10-producing CD19(+) CD1d(hi) B cells, which can suppress allergic lung inflammation via T regulatory cells.

  8. Ligation of TLR7 on CD19(+) CD1d(hi) B cells suppresses allergic lung inflammation via regulatory T cells.

    PubMed

    Khan, Adnan R; Amu, Sylvie; Saunders, Sean P; Hams, Emily; Blackshields, Gordon; Leonard, Martin O; Weaver, Casey T; Sparwasser, Tim; Sheils, Orla; Fallon, Padraic G

    2015-06-01

    B cells have been described as having the capacity to regulate cellular immune responses and suppress inflammatory processes. One such regulatory B-cell population is defined as IL-10-producing CD19(+) CD1d(hi) cells. Previous work has identified an expansion of these cells in mice infected with the helminth, Schistosoma mansoni. Here, microarray analysis of CD19(+) CD1d(hi) B cells from mice infected with S. mansoni demonstrated significantly increased Tlr7 expression, while CD19(+) CD1d(hi) B cells from uninfected mice also demonstrated elevated Tlr7 expression. Using IL-10 reporter, Il10(-/-) and Tlr7(-/-) mice, we formally demonstrate that TLR7 ligation of CD19(+) CD1d(hi) B cells increases their capacity to produce IL-10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7-elicited CD19(+) CD1d(hi) B cells reduced airway inflammation and associated airway hyperresponsiveness. Using DEREG mice to deplete FoxP3(+) T regulatory cells in allergen-sensitized mice, we show that that TLR7-elicited CD19(+) CD1d(hi) B cells suppress airway hyperresponsiveness via a T regulatory cell dependent mechanism. These studies identify that TLR7 stimulation leads to the expansion of IL-10-producing CD19(+) CD1d(hi) B cells, which can suppress allergic lung inflammation via T regulatory cells. PMID:25763771

  9. Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-β.

    PubMed

    Palomares, O; Martín-Fontecha, M; Lauener, R; Traidl-Hoffmann, C; Cavkaytar, O; Akdis, M; Akdis, C A

    2014-12-01

    The prevalence of allergic diseases has significantly increased in industrialized countries. Allergen-specific immunotherapy (AIT) remains as the only curative treatment. The knowledge about the mechanisms underlying healthy immune responses to allergens, the development of allergic reactions and restoration of appropriate immune responses to allergens has significantly improved over the last decades. It is now well-accepted that the generation and maintenance of functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg) cells are essential for healthy immune responses to environmental proteins and successful AIT. Treg cells comprise different subsets of T cells with suppressive capacity, which control the development and maintenance of allergic diseases by various ways of action. Molecular mechanisms of generation of Treg cells, the identification of novel immunological organs, where this might occur in vivo, such as tonsils, and related epigenetic mechanisms are starting to be deciphered. The key role played by the suppressor cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β produced by functional Treg cells during the generation of immune tolerance to allergens is now well established. Treg and Breg cells together have a role in suppression of IgE and induction of IgG4 isotype allergen-specific antibodies particularly mediated by IL-10. Other cell types such as subsets of dendritic cells, NK-T cells and natural killer cells producing high levels of IL-10 may also contribute to the generation of healthy immune responses to allergens. In conclusion, better understanding of the immune regulatory mechanisms operating at different stages of allergic diseases will significantly help the development of better diagnostic and predictive biomarkers and therapeutic interventions.

  10. International union against tuberculosis and lung disease (IUATLD): initiatives in non-tuberculous lung disease.

    PubMed

    Becklake, M R

    1995-12-01

    IUATLD initiatives in non-tuberculous lung disease developed in the late 1970s, coincident with improving tuberculosis control, and have targeted acute respiratory infections in children and chronic airways disease in adults and in children. The focus has been on methodology and the tools required to document the distribution and determinants of disease, and is illustrated in data gathered in African populations. Instruments developed include a simplified method of measuring bronchial hyper-reactivity and an asthma questionnaire Non-standard methods of questionnaire administration have also been validated, methods which are appropriate for use in the burgeoning urban communities and workforces of sub-Saharan Africa made up of rural migrants from different tribes and language groups. In addition, a review of reference values available for interpreting lung function in sub-Saharan African populations indicates a need to take into account a secular trend over the last two decades towards higher spirometric values. In the published data from Africa, not inconsiderable between-country differences are evident in the prevalence of chronic bronchitis in adults and of asthma in children. In addition, rates for childhood asthma were consistently higher in urban vs rural communities, with environmental factors playing an important role as well as being locally specific. Not only does the burden of morbidity attributable to both the chronic airway diseases reviewed justify past IUATLD initiatives in non-tuberculous lung disease, but it also argues that future initiatives should focus on investigating between- and within-country differences using a standardized methodology, with a view to identifying local environmental determinants susceptible to intervention and control. Curbing tobacco use is clearly important, not only to benefit the health of adult smokers for whom the ill-health consequences have long been recognized, but, and more important, to protect the health of

  11. The biodiversity hypothesis and allergic disease: world allergy organization position statement.

    PubMed

    Haahtela, Tari; Holgate, Stephen; Pawankar, Ruby; Akdis, Cezmi A; Benjaponpitak, Suwat; Caraballo, Luis; Demain, Jeffrey; Portnoy, Jay; von Hertzen, Leena

    2013-01-31

    Biodiversity loss and climate change secondary to human activities are now being associated with various adverse health effects. However, less attention is being paid to the effects of biodiversity loss on environmental and commensal (indigenous) microbiotas. Metagenomic and other studies of healthy and diseased individuals reveal that reduced biodiversity and alterations in the composition of the gut and skin microbiota are associated with various inflammatory conditions, including asthma, allergic and inflammatory bowel diseases (IBD), type1 diabetes, and obesity. Altered indigenous microbiota and the general microbial deprivation characterizing the lifestyle of urban people in affluent countries appear to be risk factors for immune dysregulation and impaired tolerance. The risk is further enhanced by physical inactivity and a western diet poor in fresh fruit and vegetables, which may act in synergy with dysbiosis of the gut flora. Studies of immigrants moving from non-affluent to affluent regions indicate that tolerance mechanisms can rapidly become impaired in microbe-poor environments. The data on microbial deprivation and immune dysfunction as they relate to biodiversity loss are evaluated in this Statement of World Allergy Organization (WAO). We propose that biodiversity, the variability among living organisms from all sources are closely related, at both the macro- and micro-levels. Loss of the macrodiversity is associated with shrinking of the microdiversity, which is associated with alterations of the indigenous microbiota. Data on behavioural means to induce tolerance are outlined and a proposal made for a Global Allergy Plan to prevent and reduce the global allergy burden for affected individuals and the societies in which they live.

  12. Importance of indoor allergens in the induction of allergy and elicitation of allergic disease.

    PubMed

    Custovic, A; Simpson, A; Woodcock, A

    1998-01-01

    During the last few decades, many countries have experienced an increase in the prevalence and severity of asthma. Over the same period, the population in the developed world has retreated indoors, and homes have become better insulated and more energy efficient, resulting in a warm and humid environment with low ventilation rates, ideally suited to house-dust-mite population growth throughout the year. Increasing exposure and increasing sensitivity to indoor allergens represent a progressively higher risk factor for the development of asthma. The development of sensitivity to indoor allergens and the symptoms and severity of asthma in later childhood are directly related to the exposure to allergens in infancy. It was relatively straightforward to demonstrate a quantitative linear dose-response relationship between exposure to house-dust-mite allergens and subsequent sensitization. However, showing the same for exposure and asthma severity has been more difficult, as the relationship between exposure and asthma symptoms in already sensitized individuals is much more complex than in the case of exposure and sensitization. Nevertheless, sensitized individuals are likely to have more severe asthma if exposed to high allergen levels than if their level of exposure is low. Sensitization to house-dust mites is a major independent risk factor for asthma in all areas where climate is conducive to mite population growth. The relevance of allergens other that mite is not consistent between different areas, and depends on the climate, habits, and socio-economic features of the local community. It would appear that presence of mite allergens in homes "overshadows" other allergens (e.g., cat, dog, or cockroach) as a risk factor for sensitization and subsequent development of allergic disease. It is possible that this is the consequence of the difference in inherent potency between allergen sources, and the question of why mite allergens are so potent in inducing sensitization

  13. The biodiversity hypothesis and allergic disease: world allergy organization position statement

    PubMed Central

    2013-01-01

    Biodiversity loss and climate change secondary to human activities are now being associated with various adverse health effects. However, less attention is being paid to the effects of biodiversity loss on environmental and commensal (indigenous) microbiotas. Metagenomic and other studies of healthy and diseased individuals reveal that reduced biodiversity and alterations in the composition of the gut and skin microbiota are associated with various inflammatory conditions, including asthma, allergic and inflammatory bowel diseases (IBD), type1 diabetes, and obesity. Altered indigenous microbiota and the general microbial deprivation characterizing the lifestyle of urban people in affluent countries appear to be risk factors for immune dysregulation and impaired tolerance. The risk is further enhanced by physical inactivity and a western diet poor in fresh fruit and vegetables, which may act in synergy with dysbiosis of the gut flora. Studies of immigrants moving from non-affluent to affluent regions indicate that tolerance mechanisms can rapidly become impaired in microbe-poor environments. The data on microbial deprivation and immune dysfunction as they relate to biodiversity loss are evaluated in this Statement of World Allergy Organization (WAO). We propose that biodiversity, the variability among living organisms from all sources are closely related, at both the macro- and micro-levels. Loss of the macrodiversity is associated with shrinking of the microdiversity, which is associated with alterations of the indigenous microbiota. Data on behavioural means to induce tolerance are outlined and a proposal made for a Global Allergy Plan to prevent and reduce the global allergy burden for affected individuals and the societies in which they live. PMID:23663440

  14. Connective tissue disease-related interstitial lung disease.

    PubMed

    Demoruelle, M Kristen; Mittoo, Shikha; Solomon, Joshua J

    2016-02-01

    Interstitial lung disease (ILD) is commonly present in patients with an underlying connective tissue disease (CTD), particularly those with systemic sclerosis, rheumatoid arthritis, and inflammatory myositis. The clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. Distinguishing features in the clinical, radiographic, and histopathologic characteristics of CTD-ILD subsets can predict prognosis and treatment response. Treatment often consists of combinations of immunosuppressive medications, but there is a paucity of guidance in the literature to help clinicians determine appropriate screening and management of CTD-ILD. As such, there is a critical need for studies that can elucidate the natural history of the CTD-ILD, as well as clarify optimal therapies for CTD patients with ILD. PMID:27421215

  15. Rheumatoid arthritis associated interstitial lung disease: a review.

    PubMed

    Assayag, Deborah; Lee, Joyce S; King, Talmadge E

    2014-01-01

    Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

  16. Scintigraphic perfusion patterns in patients with diffuse lung disease

    SciTech Connect

    Newman, G.E.; Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

    1982-04-01

    Perfusion scintigrams of 55 patients with radiographic evidence of diffuse lung disease were reviewed. Thirty-nine had acute and/or chronic changes caused by congestive heart failure, and 16 had diffuse reticulonodular disease. A normal or near-normal perfusion pattern was seen in 40/55 (73%), and this finding was equally common in the two groups. The authors conclude that perfusion scintigraphy is useful in excluding pulmonary embolism in patients with radiographic evidence of diffuse, symmetrical lung disease.

  17. Allergic Conjunctivitis

    MedlinePlus

    ... water. This is called conjunctivitis, also known as “pink eye.” Causes & Risk Factors What causes allergic conjunctivitis? ... example, if you are allergic to pollen or mold, stay indoors when pollen and mold levels are ...

  18. Interstitial lung disease in infancy: A general approach.

    PubMed

    Hines, Erica J; Walsh, Mark; Armes, Jane E; Douglas, Tonia; Chawla, Jasneek

    2016-04-01

    Childhood Interstitial lung disease (chILD) is an umbrella term used to define a broad range of rare, diffuse pulmonary disorders with altered interstitial structure that leads to abnormal gas exchange. Presentation of chILD in infancy can be difficult to differentiate from other common causes of diffuse lung disease. This article aimed at paediatricians provides an overview of interstitial lung disease presenting in infancy and includes key clinical features, a suggested approach to investigation and a summary of management. An overview of three clinical cases has been included to demonstrate the diagnostic approach, characteristic investigation findings and varied clinical outcomes.

  19. Interstitial lung disease associated with vindesine and radiation therapy for carcinoma of the lung

    SciTech Connect

    Bott, S.J.; Stewart, F.M.; Prince-Fiocco, M.A.

    1986-07-01

    Diffuse interstitial lung disease and pulmonary fibrosis occurred after the use of vindesine and radiation therapy in a patient with squamous cell carcinoma of the lung. Clinical improvement occurred after the drug was discontinued and corticosteroid therapy was initiated. Review of the literature reveals no previously reported cases of pulmonary toxicity due to vindesine when used alone or in combination with other therapeutic modalities.

  20. Clinical spectrum of chronic interstitial lung disease in children.

    PubMed

    Fan, L L; Mullen, A L; Brugman, S M; Inscore, S C; Parks, D P; White, C W

    1992-12-01

    To describe the clinical spectrum of interstitial lung disease in children, we reviewed our experience with 48 patients during a 12-year period. Most patients initially had typical findings of restrictive lung disease and hypoxemia. Growth failure or pulmonary hypertension or both were found in more than one third. Specific diagnosis, made in 35 patients (70%), most often required invasive studies, particularly open lung biopsy. Although the diagnostic yield from open lung biopsy was high, the diagnosis of many patients remained uncertain. Many different disorders were encountered. The response to corticosteroids, bronchodilators, and chloroquine was inconsistent. Six patients died, five within 1 year after the initial evaluation. The spectrum of pediatric interstitial lung disease includes a large, heterogeneous group of rare disorders associated with high morbidity and mortality rates.

  1. Genetically manipulated mouse models of lung disease: potential and pitfalls

    PubMed Central

    Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

    2012-01-01

    Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

  2. [Why screen for lung cancer in patients with arterial disease?].

    PubMed

    Lederlin, M; Trédaniel, J; Priollet, P

    2015-12-01

    Lung cancer remains the leading cause of cancer death in France. Such a prognosis is explained by late diagnosis at a metastatic stage for half of the patients. Tobacco is the main risk factor for lung cancer, as it is for peripheral arterial disease. A review of literature shows that between 2.3% and 19% of patients with arterial disease also have lung cancer. When lung cancer is detected after treatment of arterial disease, it is at an advanced stage. But it can be diagnosed at an early stage when it is searched simultaneously with arterial disease treatment. There is no recommendation for lung cancer screening specifically for patients with arterial disease. However individual screening based on an annual low-dose chest scan is proposed for smokers meeting the criteria defined by the study of the National Lung Screening Trial (NLST). Such screening has two disadvantages : the high number of false positives and the irradiation induced by the accumulation of examinations. The ISET method would alternatively help to identify circulating tumor cells on a simple blood test for subjects not yet at solid tumor stage, provided this method be subject to multicentric validation. Thus one could consider that the management of a patient with arterial disease meeting NLST criteria should be accompanied with screening for lung cancer by searching for tumor cells associated with low-dose scanner.

  3. Nutrition, growth, and allergic diseases among very preterm infants after hospital discharge.

    PubMed

    Zachariassen, Gitte

    2013-02-01

    The aims of this PhD thesis were: 1. Primarily to investigate the effect, of adding human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge, on growth until 1 year corrected age (CA) 2. Secondarily to describe breastfeeding rate and factors associated with breastfeeding among very preterm infants at hospital discharge. 3. To describe possible feeding-problems during the intervention-period, and allergic diseases during the first year of life, among very preterm infants related to their nutrition after hospital discharge. 4. To describe the content of macronutrients in human milk from mothers delivering very preterm. This PhD thesis is based on a prospective, randomized, and controlled interventional birth cohort study. A total of 633 very preterm infants with a gestational age (GA) ≤ 32 + 0 weeks were recruited consecutively from July 2004 until August 2008 of whom 157 were excluded due to diseases or circumstances influencing nutrition. Further 156 refused participation in the interventional part of the study, but data on breastfeeding, weight, and some epidemiological data until discharge were available. Results on breastfeeding rate at discharge were therefore based on data from 478 infants, and parents of 320 infants accepted participation in the intervention study. Of these 320 infants, 207 were exclusively breastfed and they were shortly before hospital discharge randomized to either breastfeeding without (group A) or with fortification (group B) until 4 months CA. Infants (n = 113) who were bottle-fed at discharge (group C) were given a preterm formula (PF) until 4 months CA. Infants were examined at the outpatient clinics at term, and at 2, 4, 6, and 12 months CA, where parameters on growth, allergic diseases, possible feeding problems, blood-samples, and milk samples were obtained. Data on duration of exclusively breastfeeding and time of introduction to formula and/or complementary food were also recorded

  4. Ventilatory strategies in obstructive lung disease.

    PubMed

    Parrilla, Francisco José; Morán, Indalecio; Roche-Campo, Ferran; Mancebo, Jordi

    2014-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation (EFL) due to progressive airflow obstruction. The various mechanisms that cause EFL are central to understanding the physiopathology of COPD. At the end of expiration, dynamic inflation may occur due to incomplete emptying the lungs. This "extra" volume increases the alveolar pressure at the end of the expiration, resulting in auto-positive end-expiratory pressure (PEEP) or PEEPi. Acute exacerbations of COPD may result in increased airway resistance and inspiratory effort, further leading to dynamic hyperinflation. COPD exacerbations may be triggered by environmental exposures, infections (viral and bacterial), or bronchial inflammation, and may result in worsening respiratory failure requiring mechanical ventilation (MV). Acute exacerbations of COPD need to be distinguished from other events such as cardiac failure or pulmonary emboli. Strategies to treat acute respiratory failure (ARF) in COPD patients include noninvasive ventilation (NIV), pressure support ventilation, and tracheal intubation with MV. In this review, we discuss invasive and noninvasive techniques to address ARF in this patient population. When invasive MV is used, settings should be adjusted in a way that minimizes hyperinflation, while providing reasonable gas exchange, respiratory muscle rest, and proper patient-ventilator interaction. Further, weaning from MV may be difficult in these patients, and factors amenable to pharmacological correction (such as increased bronchial resistance, tracheobronchial infections, and heart failure) are to be systematically searched and treated. In selected patients, early use of NIV may hasten the process of weaning from MV and improve outcomes.

  5. Neurogenic inflammation in lung disease: burnt out?

    PubMed

    Rogers, D F

    1997-01-01

    Neurogenic inflammation results from activation of sensory nerves which, acting in an 'efferent' manner, release sensory neuropeptides to induce a wide variety of physiological and immunological responses. This process is easy to demonstrate experimentally in the airways of small laboratory animal species but in human airways is equivocal and, at best, minor compared with cholinergic neural control. Nevertheless, sensory neuropeptides (calcitonin gene-related peptide and the tachykinins, substance P and neurokinin A) induce airway responses in both laboratory animals and humans which suggest a potential for sensory-efferent control of human airways. In addition, there is indirect evidence for an increased 'expression' of sensory nerves and tachykinin receptors in asthma and bronchitis, which indicates that neurogenic inflammation contributes to pathophysiology of these airway conditions. In contrast, clinical trials using different classes of drugs to inhibit sensory nerve responses have failed to resolve whether neurogenic inflammation is involved in asthma, although there are concerns about the relevance of some of these studies. In contrast to their involvement in airway neurogenic inflammation, sensory nerves may be important in initiating protective reflexes, including coughing and sneezing, acting via their afferent pathways. Thus, although flickering, the concept of neurogenic inflammation in lung disease is not yet burnt out. However, it needs the rekindling of interest which re-evaluation as a protective process may bring, together with data from more appropriate clinical studies in asthma and chronic bronchitis. PMID:17657611

  6. Ventilatory strategies in obstructive lung disease.

    PubMed

    Parrilla, Francisco José; Morán, Indalecio; Roche-Campo, Ferran; Mancebo, Jordi

    2014-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation (EFL) due to progressive airflow obstruction. The various mechanisms that cause EFL are central to understanding the physiopathology of COPD. At the end of expiration, dynamic inflation may occur due to incomplete emptying the lungs. This "extra" volume increases the alveolar pressure at the end of the expiration, resulting in auto-positive end-expiratory pressure (PEEP) or PEEPi. Acute exacerbations of COPD may result in increased airway resistance and inspiratory effort, further leading to dynamic hyperinflation. COPD exacerbations may be triggered by environmental exposures, infections (viral and bacterial), or bronchial inflammation, and may result in worsening respiratory failure requiring mechanical ventilation (MV). Acute exacerbations of COPD need to be distinguished from other events such as cardiac failure or pulmonary emboli. Strategies to treat acute respiratory failure (ARF) in COPD patients include noninvasive ventilation (NIV), pressure support ventilation, and tracheal intubation with MV. In this review, we discuss invasive and noninvasive techniques to address ARF in this patient population. When invasive MV is used, settings should be adjusted in a way that minimizes hyperinflation, while providing reasonable gas exchange, respiratory muscle rest, and proper patient-ventilator interaction. Further, weaning from MV may be difficult in these patients, and factors amenable to pharmacological correction (such as increased bronchial resistance, tracheobronchial infections, and heart failure) are to be systematically searched and treated. In selected patients, early use of NIV may hasten the process of weaning from MV and improve outcomes. PMID:25111641

  7. How changes in nutrition have influenced the development of allergic diseases in childhood

    PubMed Central

    2012-01-01

    The increasing prevalence of allergic diseases in childhood in the last decades could be linked to concomitant dietary changes, especially with the modified and lower consumption of fruit, vegetables and minerals. The consumption of these foods by pregnant women and children in the first years of life seems to be associated with a reduced risk of asthma and related symptoms. Foods that can prevent the development of wheezing through their antioxidant effects contain vitamin C and selenium; blood levels of these elements correlate negatively with the risk of wheezing. Intake of vitamin E during pregnancy also appears to be correlated with a reduced risk of wheezing for the unborn child. Similarly, low intake of zinc and carotenoids by pregnant women is associated with an increased risk of wheezing and asthma in childhood. Fiber also has anti-inflammatory properties and protective effects against allergic diseases such as atopic dermatitis and asthma. The consumption of fat influences the development of the airways. Populations in Western countries have increased their consumption of n-6 PUFAs and, in parallel, reduced n-3 PUFAs. This has led to decreased production of PGE2, which is believed to have a protective effect against inflammation of the airways. Conflicting hypotheses also concern vitamin D; both an excess and a deficiency of vitamin D, in fact, have been associated with an increased risk of asthma. Further studies on the role of these substances are necessary before any conclusions can be drawn on a clinical level. Astratto La crescente prevalenza negli ultimi decenni delle malattie allergiche in età pediatrica potrebbe essere legata a concomitanti cambiamenti nella dieta, in particolare alla minore e modificata introduzione di frutta, verdura e minerali. Il consumo di questi alimenti da parte delle donne in gravidanza e dei bambini nei primi anni di vita sembra essere associato ad un ridotto rischio di asma e di sintomi correlati. Gli alimenti che

  8. Lung cancer screening in patients with chronic obstructive pulmonary disease

    PubMed Central

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo

    2016-01-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

  9. Usefulness of texture features for segmentation of lungs with severe diffuse interstitial lung disease

    NASA Astrophysics Data System (ADS)

    Wang, Jiahui; Li, Feng; Li, Qiang

    2010-03-01

    We developed an automated method for the segmentation of lungs with severe diffuse interstitial lung disease (DILD) in multi-detector CT. In this study, we would like to compare the performance levels of this method and a thresholdingbased segmentation method for normal lungs, moderately abnormal lungs, severely abnormal lungs, and all lungs in our database. Our database includes 31 normal cases and 45 abnormal cases with severe DILD. The outlines of lungs were manually delineated by a medical physicist and confirmed by an experienced chest radiologist. These outlines were used as reference standards for the evaluation of the segmentation results. We first employed a thresholding technique for CT value to obtain initial lungs, which contain normal and mildly abnormal lung parenchyma. We then used texture-feature images derived from co-occurrence matrix to further segment lung regions with severe DILD. The segmented lung regions with severe DILD were combined with the initial lungs to generate the final segmentation results. We also identified and removed the airways to improve the accuracy of the segmentation results. We used three metrics, i.e., overlap, volume agreement, and mean absolute distance (MAD) between automatically segmented lung and reference lung to evaluate the performance of our segmentation method and the thresholding-based segmentation method. Our segmentation method achieved a mean overlap of 96.1%, a mean volume agreement of 98.1%, and a mean MAD of 0.96 mm for the 45 abnormal cases. On the other hand the thresholding-based segmentation method achieved a mean overlap of 94.2%, a mean volume agreement of 95.8%, and a mean MAD of 1.51 mm for the 45 abnormal cases. Our new method obtained higher performance level than the thresholding-based segmentation method.

  10. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2009-02-01

    This review highlights some of the research advances in anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported in the Journal in 2008. Key epidemiologic observations include a rise in anaphylaxis in a population-based study and lower rates of peanut allergy in Israel, where infants consume peanut early compared with the United Kingdom, where dietary introduction is generally delayed. Advances in food allergy diagnosis include IgE epitope mapping that discloses the likelihood and severity of allergy; studies correlating likelihood of clinical reactivity on the basis of food-specific IgE to sesame, peanut, milk, and tree nuts; and an observation that a low baseline angiotensin-converting enzyme level may be associated with having pharyngeal edema during a reaction. Molecular, immunologic, and genetic studies are discerning pathways that are key in development of food allergy, identifying new modalities to interrupt mast cell degranulation, and elucidating risks associated with penicillin allergy. Regarding treatment, clinical studies show a majority of children with milk and egg allergy tolerate these proteins in modest amounts when they are extensively heated in baked goods, and studies show promise for oral immunotherapy to treat milk allergy and sublingual immunotherapy for honey bee venom hypersensitivity. The importance of skin barrier dysfunction has continued to be highlighted in the pathophysiology of atopic dermatitis (AD). Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to develop viral and bacterial infection. New therapeutic approaches to AD, urticaria, and angioedema have been reported including use of probiotics, biologics, vitamin D, and skin barrier creams.

  11. Effects of climate change on environmental factors in respiratory allergic diseases.

    PubMed

    D'Amato, G; Cecchi, L

    2008-08-01

    A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by human activity, have an impact on the biosphere and the human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between asthma and environmental factors, such as meteorological variables, airborne allergens and air pollution. However, there is also considerable evidence that subjects affected by asthma are at an increased risk of developing obstructive airway exacerbations with exposure to gaseous and particulate components of air pollution. It is not easy to evaluate the impact of climate change and air pollution on the prevalence of asthma in general and on the timing of asthma exacerbations. However, the global rise in asthma prevalence and severity suggests that air pollution and climate changes could be contributing. Pollen allergy is frequently used to study the interrelationship between air pollution, rhinitis and bronchial asthma. Epidemiological studies have demonstrated that urbanization, high levels of vehicle emissions and westernized lifestyle are correlated to an increase in the frequency of pollen-induced respiratory allergy, prevalent in people who live in urban areas compared with those who live in rural areas. Meteorological factors (temperature, wind speed, humidity, etc.) along with their climatological regimes (warm or cold anomalies and dry or wet periods, etc.), can affect both biological and chemical components of this interaction. In addition, by inducing airway inflammation, air pollution overcomes the mucosal barrier priming allergen-induced responses. In conclusion, climate change might induce negative effects on respiratory allergic diseases. In particular, the increased length and severity of the pollen season, the higher occurrence of heavy precipitation events and the

  12. [Basic lung ultrasound. Part 2. Parenchymal diseases].

    PubMed

    de la Quintana Gordon, F B; Nacarino Alcorta, B; Fajardo Pérez, M

    2015-01-01

    In this second part, an analysis is made of the pathology of lung parenchyma. This text is structured into different sections, including the study of atelectasias, pneumonia and abscess, interstitial/alveolar or Blines patterns, and finally an analysis is made of pulmonary embolism. With this second part, the basic knowledge to develop lung ultrasound in the anesthesia department has been presented.

  13. [Basic lung ultrasound. Part 2. Parenchymal diseases].

    PubMed

    de la Quintana Gordon, F B; Nacarino Alcorta, B; Fajardo Pérez, M

    2015-01-01

    In this second part, an analysis is made of the pathology of lung parenchyma. This text is structured into different sections, including the study of atelectasias, pneumonia and abscess, interstitial/alveolar or Blines patterns, and finally an analysis is made of pulmonary embolism. With this second part, the basic knowledge to develop lung ultrasound in the anesthesia department has been presented. PMID:25708093

  14. Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

    SciTech Connect

    Bernard, Alfred Nickmilder, Marc; Dumont, Xavier

    2015-07-15

    It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

  15. Management of Allergic Rhinitis

    PubMed Central

    Sausen, Verra O.; Marks, Katherine E.; Sausen, Kenneth P.; Self, Timothy H.

    2005-01-01

    Allergic rhinitis is the most common chronic childhood disease. Reduced quality of life is frequently caused by this IgE-mediated disease, including sleep disturbance with subsequent decreased school performance. Asthma and exercise-induced bronchospasm are commonly seen concurrently with allergic rhinitis, and poorly controlled allergic rhinitis negatively affects asthma outcomes. Nonsedating antihistamines or intranasal azelastine are effective agents to manage allergic rhinitis, often in combination with oral decongestants. For moderate to severe persistent disease, intranasal corticosteroids are the most effiective agents. Some patients require concomitant intranasal corticosteroids and nonsedating antihistamines for optimal management. Other available agents include leukotriene receptor antagonists, intranasal cromolyn, intranasal ipratropium, specific immunotherapy, and anti-IgE therapy. PMID:23118635

  16. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease

    PubMed Central

    Kottyan, Leah C.; Davis, Benjamin P.; Sherrill, Joseph D.; Liu, Kan; Rochman, Mark; Kaufman, Kenneth; Weirauch, Matthew T.; Vaughn, Samuel; Lazaro, Sara; Rupert, Andrew M.; Kohram, Mojtaba; Stucke, Emily M.; Kemme, Katherine A.; Magnusen, Albert; He, Hua; Dexheimer, Phillip; Chehade, Mirna; Wood, Robert A.; Pesek, Robbie D.; Vickery, Brian P.; Fleischer, David M.; Lindbad, Robert; Sampson, Hugh A.; Mukkada, Vince; Putnam, Phil E.; Abonia, J. Pablo; Martin, Lisa J.; Harley, John B.; Rothenberg, Marc E.

    2014-01-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in European EoE cases and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replication of the 5q22 locus (meta-analysis p = 1.9×10−16), we identified association at 2p23 (encoding CAPN14, p = 2.5×10−10). CAPN14 was specifically expressed in the esophagus, dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to IL-13, and located in an epigenetic hotspot modified by IL-13. There was enriched esophageal expression for the genes neighboring the top 208 EoE sequence variants. Multiple allergic sensitization loci were associated with EoE susceptibility (4.8×10−2 < p < 5.1×10−11). We propose a model that elucidates the tissue specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13–inducible esophageal response involving CAPN14. PMID:25017104

  17. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    PubMed

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. PMID:25929952

  18. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    PubMed

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease.

  19. Bioactive extracellular matrix fragments in lung health and disease.

    PubMed

    Gaggar, Amit; Weathington, Nathaniel

    2016-09-01

    The extracellular matrix (ECM) is the noncellular component critical in the maintenance of organ structure and the regulation of tissue development, organ structure, and cellular signaling. The ECM is a dynamic entity that undergoes continuous degradation and resynthesis. In addition to compromising structure, degradation of the ECM can liberate bioactive fragments that cause cellular activation and chemotaxis of a variety of cells. These fragments are termed matrikines, and their cellular activities are sentinel in the development and progression of tissue injury seen in chronic lung disease. Here, we discuss the matrikines that are known to be active in lung biology and their roles in lung disease. We also consider the use of matrikines as disease markers and potential therapeutic targets in lung disease. PMID:27584731

  20. Radiation-induced heart disease in lung cancer radiotherapy

    PubMed Central

    Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

    2016-01-01

    Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

  1. Asbestos lung burden and disease patterns in man

    SciTech Connect

    Churg, A.

    1993-12-31

    This article discusses the relationship between disease and asbestos burden in the human lung. The differences in this relationship for various types of asbestos are also discussed. Finally the outstanding issues in the field of asbestos research and disease are presented including the following: discrepancies between data derived from animal experiments, predictions based on mathematical models, and data derived from actual analysis of autopsied human lungs. 75 refs., 3 figs., 3 tab.

  2. Clara cells drive eosinophil accumulation in allergic asthma.

    PubMed

    Sonar, S S; Ehmke, M; Marsh, L M; Dietze, J; Dudda, J C; Conrad, M L; Renz, H; Nockher, W A

    2012-02-01

    Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.

  3. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives.

    PubMed

    Ryu, Yon Ju; Koh, Won-Jung; Daley, Charles L

    2016-04-01

    Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article. PMID:27066084

  4. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives

    PubMed Central

    Ryu, Yon Ju; Koh, Won-Jung

    2016-01-01

    Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article. PMID:27066084

  5. Adenosine signaling and the regulation of chronic lung disease

    PubMed Central

    Zhou, Yang; Schneider, Daniel J.; Blackburn, Michael R.

    2009-01-01

    Chronic lung diseases such as asthma, chronic obstructive pulmonary disease and interstitial lung disease are characterized by inflammation and tissue remodeling processes that compromise pulmonary function. Adenosine is produced in the inflamed and damaged lung where it plays numerous roles in the regulation of inflammation and tissue remodeling. Extracellular adenosine serves as an autocrine and paracrine signaling molecule by engaging cell surface adenosine receptors. Preclinical and cellular studies suggest that adenosine plays an anti-inflammatory role in processes associated with acute lung disease, where activation of the A2AR and A2BR have promising implications for the treatment of these disorders. In contrast, there is growing evidence that adenosine signaling through the A1R, A2BR and A3R may serve pro-inflammatory and tissue remodeling functions in chronic lung diseases. This review discusses the current progress of research efforts and clinical trials aimed at understanding the complexities of this signaling pathway as they pertain to the development of treatment strategies for chronic lung diseases. PMID:19426761

  6. Integrin α3 Mutations with Kidney, Lung, and Skin Disease

    PubMed Central

    Has, Cristina; Spartà, Giuseppina; Kiritsi, Dimitra; Weibel, Lisa; Moeller, Alexander; Vega-Warner, Virginia; Waters, Aoife; He, Yinghong; Anikster, Yair; Esser, Philipp; Straub, Beate K.; Hausser, Ingrid; Bockenhauer, Detlef; Dekel, Benjamin; Hildebrandt, Friedhelm; Bruckner-Tuderman, Leena; Laube, Guido F.

    2012-01-01

    SUMMARY Integrin α3 is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. We identified three patients with homozygous mutations in the integrin α3 gene that were associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. The patients had a multiorgan disorder that included congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The renal and respiratory features predominated, and the lung involvement accounted for the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. PMID:22512483

  7. Prevalence and risk factors of asthma and allergic diseases in primary schoolchildren living in Bushehr, Iran: phase I, III ISAAC protocol.

    PubMed

    Farrokhi, Shokrollah; Gheybi, Mohammad Kazzem; Movahhed, Ali; Dehdari, Reyhaneh; Gooya, Mostafa; Keshvari, Saman; Gholampour, Hossein; Mansourian, Zohreh; Khosravi, Yasaman; Ghahramani, Forough; Zandi, Sahar; Etemadan, Razieh; Tahmasebi, Rahim; Reaisi, Alireza; Keshmiri, Saeed; Fadaizadeh, Lida; Masjedi, Mohammad Reza

    2014-10-01

    Asthma and allergic diseases present a major health burden. Information on the prevalence of these diseases indicates that these diseases are increasing in various parts of the world. It was hoped that this study would be helpful to health system policy-makers in planning allergy prevention programs in the region.The prevalence of asthma and allergic diseases and relation between the various risk factors involved were assessed among schoolchildren in the city of Bushehr, Iran. The ISAAC Phase I and III questionnaires were completed by parents of 1280 children aged 6-7 years and self-completed by 1115 students aged 13-14 years.The prevalence of atopic eczema, allergic rhinitis and asthma among 6-7 year-old students were 12.1%, 11.8% and 6.7%, respectively. While, the prevalence of these diseases among 13-14 year-old students were found to be 19%, 30% and 7.6%, respectively. There was an association between asthma and allergic rhinitis as well as eczema (p<0.05). Consumption of fast food as a risk factor was significantly associated with asthma (p=0.03).The prevalence of asthma and allergic diseases was high among schoolchildren in the city of Bushehr, Iran. Also an association was observed between the fast food consumption and asthma. PMID:25150076

  8. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function.

    PubMed

    Kinder, Brent W; Shariat, Cyrus; Collard, Harold R; Koth, Laura L; Wolters, Paul J; Golden, Jeffrey A; Panos, Ralph J; King, Talmadge E

    2010-04-01

    Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.

  9. Farmer's Lung: Causes and Symptoms of Mold and Dust Induced Respiratory Illness

    MedlinePlus

    ... Educational Resources Farmer's Lung: Causes and Symptoms of Mold and Dust Induced Respiratory Illness ID 442-602 ( ... noninfectious allergic disease that is caused by inhaling mold spores in the dust from moldy hay, straw, ...

  10. Effect of thermoneutral housing on fungal-induced respiratory allergic disease in mice

    EPA Science Inventory

    Climate change is projected to increase the number of fungal, bacterial, and pollen agents both indoors and outdoors and may become a significant health impact. Combined with the thermal stress from a rise in global temperatures, it is important to consider how respiratory allerg...

  11. Rapamycin decreases airway remodeling and hyperreactivity in a transgenic model of noninflammatory lung disease.

    PubMed

    Kramer, Elizabeth L; Hardie, William D; Mushaben, Elizabeth M; Acciani, Thomas H; Pastura, Patricia A; Korfhagen, Thomas R; Hershey, Gurjit Khurana; Whitsett, Jeffrey A; Le Cras, Timothy D

    2011-12-01

    Airway hyperreactivity (AHR) and remodeling are cardinal features of asthma and chronic obstructive pulmonary disease. New therapeutic targets are needed as some patients are refractory to current therapies and develop progressive airway remodeling and worsening AHR. The mammalian target of rapamycin (mTOR) is a key regulator of cellular proliferation and survival. Treatment with the mTOR inhibitor rapamycin inhibits inflammation and AHR in allergic asthma models, but it is unclear if rapamycin can directly inhibit airway remodeling and AHR, or whether its therapeutic effects are entirely mediated through immunosuppression. To address this question, we utilized transforming growth factor-α (TGF-α) transgenic mice null for the transcription factor early growth response-1 (Egr-1) (TGF-α Tg/Egr-1(ko/ko) mice). These mice develop airway smooth muscle thickening and AHR in the absence of altered lung inflammation, as previously reported. In this study, TGF-α Tg/Egr-1(ko/ko) mice lost body weight and developed severe AHR after 3 wk of lung-specific TGF-α induction. Rapamycin treatment prevented body weight loss, airway wall thickening, abnormal lung mechanics, and increases in airway resistance to methacholine after 3 wk of TGF-α induction. Increases in tissue damping and airway elastance were also attenuated in transgenic mice treated with rapamycin. TGF-α/Egr-1(ko/ko) mice on doxycycline for 8 wk developed severe airway remodeling. Immunostaining for α-smooth muscle actin and morphometric analysis showed that rapamycin treatment prevented airway smooth muscle thickening around small airways. Pentachrome staining, assessments of lung collagen and fibronectin mRNA levels, indicated that rapamycin also attenuated fibrotic pathways induced by TGF-α expression for 8 wk. Thus rapamycin reduced airway remodeling and AHR, demonstrating an important role for mTOR signaling in TGF-α-induced/EGF receptor-mediated reactive airway disease. PMID:21903885

  12. Rapamycin decreases airway remodeling and hyperreactivity in a transgenic model of noninflammatory lung disease.

    PubMed

    Kramer, Elizabeth L; Hardie, William D; Mushaben, Elizabeth M; Acciani, Thomas H; Pastura, Patricia A; Korfhagen, Thomas R; Hershey, Gurjit Khurana; Whitsett, Jeffrey A; Le Cras, Timothy D

    2011-12-01

    Airway hyperreactivity (AHR) and remodeling are cardinal features of asthma and chronic obstructive pulmonary disease. New therapeutic targets are needed as some patients are refractory to current therapies and develop progressive airway remodeling and worsening AHR. The mammalian target of rapamycin (mTOR) is a key regulator of cellular proliferation and survival. Treatment with the mTOR inhibitor rapamycin inhibits inflammation and AHR in allergic asthma models, but it is unclear if rapamycin can directly inhibit airway remodeling and AHR, or whether its therapeutic effects are entirely mediated through immunosuppression. To address this question, we utilized transforming growth factor-α (TGF-α) transgenic mice null for the transcription factor early growth response-1 (Egr-1) (TGF-α Tg/Egr-1(ko/ko) mice). These mice develop airway smooth muscle thickening and AHR in the absence of altered lung inflammation, as previously reported. In this study, TGF-α Tg/Egr-1(ko/ko) mice lost body weight and developed severe AHR after 3 wk of lung-specific TGF-α induction. Rapamycin treatment prevented body weight loss, airway wall thickening, abnormal lung mechanics, and increases in airway resistance to methacholine after 3 wk of TGF-α induction. Increases in tissue damping and airway elastance were also attenuated in transgenic mice treated with rapamycin. TGF-α/Egr-1(ko/ko) mice on doxycycline for 8 wk developed severe airway remodeling. Immunostaining for α-smooth muscle actin and morphometric analysis showed that rapamycin treatment prevented airway smooth muscle thickening around small airways. Pentachrome staining, assessments of lung collagen and fibronectin mRNA levels, indicated that rapamycin also attenuated fibrotic pathways induced by TGF-α expression for 8 wk. Thus rapamycin reduced airway remodeling and AHR, demonstrating an important role for mTOR signaling in TGF-α-induced/EGF receptor-mediated reactive airway disease.

  13. Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro

    2006-03-01

    IgE molecules play a crucial role in allergic respiratory diseases and may cause chronic airway inflammation in asthma through activation of effector cells via high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII) IgE receptors. Since the discovery of IgE antibodies our understanding of the mechanisms of allergy has improved to such an extent that we can differentiate allergic/atopic from intrinsic respiratory diseases. Therapeutic anti-IgE antibodies, able to reduce free IgE levels and to block the binding of IgE to FcepsilonRI without crosslinking IgE and triggering degranulation of IgE-sensitized cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (omalizumab) binds IgE at the same site as these antibodies bind FcepsilonRI and FcepsilonRII. Consequently, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the FcepsilonR1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma showed that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted effective in reducing asthma-related symptoms, decreasing corticosteroid use and improving quality of life of asthmatic patients. Recent studies show the benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled by optimal pharmacological therapy. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases such as allergic rhinitis, a favorable safety profile and a convenient dosing frequency.

  14. Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model

    PubMed Central

    2013-01-01

    Background The importance of the lung parenchyma in the pathophysiology of asthma has previously been demonstrated. Considering that nitric oxide synthases (NOS) and arginases compete for the same substrate, it is worthwhile to elucidate the effects of complex NOS-arginase dysfunction in the pathophysiology of asthma, particularly, related to distal lung tissue. We evaluated the effects of arginase and iNOS inhibition on distal lung mechanics and oxidative stress pathway activation in a model of chronic pulmonary allergic inflammation in guinea pigs. Methods Guinea pigs were exposed to repeated ovalbumin inhalations (twice a week for 4 weeks). The animals received 1400 W (an iNOS-specific inhibitor) for 4 days beginning at the last inhalation. Afterwards, the animals were anesthetized and exsanguinated; then, a slice of the distal lung was evaluated by oscillatory mechanics, and an arginase inhibitor (nor-NOHA) or vehicle was infused in a Krebs solution bath. Tissue resistance (Rt) and elastance (Et) were assessed before and after ovalbumin challenge (0.1%), and lung strips were submitted to histopathological studies. Results Ovalbumin-exposed animals presented an increase in the maximal Rt and Et responses after antigen challenge (p<0.001), in the number of iNOS positive cells (p<0.001) and in the expression of arginase 2, 8-isoprostane and NF-kB (p<0.001) in distal lung tissue. The 1400 W administration reduced all these responses (p<0.001) in alveolar septa. Ovalbumin-exposed animals that received nor-NOHA had a reduction of Rt, Et after antigen challenge, iNOS positive cells and 8-isoprostane and NF-kB (p<0.001) in lung tissue. The activity of arginase 2 was reduced only in the groups treated with nor-NOHA (p <0.05). There was a reduction of 8-isoprostane expression in OVA-NOR-W compared to OVA-NOR (p<0.001). Conclusions In this experimental model, increased arginase content and iNOS-positive cells were associated with the constriction of distal lung parenchyma

  15. Chair’s Summary: Mechanisms of Exacerbation of Lung Diseases

    PubMed Central

    Nicod, Laurent P.

    2015-01-01

    This year’s conference focused on the origins of exacerbations in chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis. Common themes emerged, with the role of viral infections being key. In addition, there were data presented supporting the role of the microbiota and microbial dysbiosis either in the gut or in the lung contributing to disease progression and the susceptibility to disease exacerbation. These effects can be amplified by the triggering of biologic cascades that include alterations in oxidative stress and inflammatory mediator release, which can be driven by epithelial cell injury or activation. PMID:26595726

  16. New insights into lung diseases using hyperpolarized gas MRI.

    PubMed

    Flors, L; Altes, T A; Mugler, J P; de Lange, E E; Miller, G W; Mata, J F; Ruset, I C; Hersman, F W

    2015-01-01

    Hyperpolarized (HP) gases are a new class of contrast agents that permit to obtain high temporal and spatial resolution magnetic resonance images (MRI) of the lung airspaces. HP gas MRI has become important research tool not only for morphological and functional evaluation of normal pulmonary physiology but also for regional quantification of pathologic changes occurring in several lung diseases. The purpose of this work is to provide an introduction to MRI using HP noble gases, describing both the basic principles of the technique and the new information about lung disease provided by clinical studies with this method. The applications of the technique in normal subjects, smoking related lung disease, asthma, and cystic fibrosis are reviewed.

  17. Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

    PubMed Central

    Hartert, Tina V.; Martinez, Fernando D.; Weiss, Scott T.; Fahy, John V.

    2014-01-01

    Asthma is a common disease with enormous public health costs, and its primary prevention is an ambitious and important goal. Understanding of how host and environmental factors interact to cause asthma is incomplete, but persistent questions about mechanisms should not stop clinical research efforts aimed at reducing the prevalence of childhood asthma. Achieving the goal of primary prevention of asthma will involve integrated and parallel sets of research activities in which mechanism-oriented studies of asthma inception proceed alongside clinical intervention studies to test biologically plausible prevention ideas. For example, continued research is needed, particularly in young children, to uncover biomarkers that identify asthma risk and provide potential targets of intervention, and to improve understanding of the role of microbial factors in asthma risk and disease initiation. In terms of clinical trials that could be initiated now or in the near future, we recommend three interventions for testing: (1) preventing asthma through prophylaxis against respiratory syncytial virus and human rhinovirus infections of the airway; (2) immune modulation, using prebiotics, probiotics, and bacterial lysates; and (3) prevention of allergen sensitization and allergic inflammation, using anti-IgE. These interventions should be tested while other, more universal prevention measures that may promote lung health are also investigated. These potential universal lung health measures include prevention of preterm delivery; reduced exposure of the fetus and young infant to environmental pollutants, including tobacco smoke; prevention of maternal and child obesity; and management of psychosocial stress. PMID:24754822

  18. Air quality and seasonal variations in consultations for respiratory, allergic, dermatological and gastrointestinal diseases in Bahrain, 2007.

    PubMed

    Hamadeh, R R; Al-Roomi, K A

    2014-06-09

    Environmental health data in Bahrain are scarce. This study in 4 governorates of Bahrain aimed to establish baseline data on the seasonal prevalence of certain disease groups that are sensitive to climate (respiratory, allergic, dermatological and non-specific gastrointestinal diseases) over a 1-year period and to record local climate and air pollutant data for the same year. A 5% sample of medical records for those who attended primary health-care centres during 2007 was taken. Visit rates for all 4 diseases had peaks, in spring and in autumn, with the lowest rates in the summer season when the average temperatures were highest and average humidity was lower. Respiratory-related visits were highest when the air concentrations of SO2 were highest. An ongoing surveillance system for climate-sensitive diseases should be initiated to monitor and relate health and environmental trends.

  19. Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease.

    PubMed

    Chiuchiolo, Maria J; Crystal, Ronald G

    2016-08-01

    Alpha-1 antitrypsin (AAT) deficiency, characterized by low plasma levels of the serine protease inhibitor AAT, is associated with emphysema secondary to insufficient protection of the lung from neutrophil proteases. Although AAT augmentation therapy with purified AAT protein is efficacious, it requires weekly to monthly intravenous infusion of AAT purified from pooled human plasma, has the risk of viral contamination and allergic reactions, and is costly. As an alternative, gene therapy offers the advantage of single administration, eliminating the burden of protein infusion, and reduced risks and costs. The focus of this review is to describe the various strategies for AAT gene therapy for the pulmonary manifestations of AAT deficiency and the state of the art in bringing AAT gene therapy to the bedside. PMID:27564673

  20. Exploring Household-level Risk Factors for Self-reported Prevalence of Allergic Diseases Among Low-income Households in Seoul, Korea

    PubMed Central

    Seo, SungChul; Paul, Christopher; Yoo, Young; Choung, Ji Tae

    2014-01-01

    Purpose Indoor risk factors for allergic diseases in low-income households in Korea have been characterized only partially. We evaluated the prevalences of atopic dermatitis, asthma, and allergic rhinitis in Seoul, Korea, to identify key housing and behavioral risk factors of low-income households. Methods Statistical analysis of the prevalence of these diseases and various risk factors was conducted using data from a 2010 Ministry of Environment household survey. Logistic regression models were generated using data from 511 low-income household apartments in districts of Seoul. Results In general, housing factors such as renovation history (P<0.1) and crowding status (P<0.01) were associated with allergic rhinitis, whereas behavioral factors such as frequency of indoor ventilation (P<0.05) and cleaning (P<0.1) were inversely correlated with atopic dermatitis. Indoor smoking was a major trigger of asthma and atopic dermatitis in low-income households (P<0.05). The presence of mold and water leakage in houses were the most important risk factors for all three diseases (P<0.05). Conclusions Various risk factors play a role in triggering allergic diseases among low-income households in Seoul, and health or environmental programs mitigating allergic diseases should be tailored to address appropriate housing or behavioral factors in target populations. PMID:25228999

  1. Animal models of beryllium-induced lung disease

    SciTech Connect

    Finch, G.L.; Hoover, M.D.; Hahn, F.F.

    1996-10-01

    The Inhalation Toxicology Research Institute (ITRI) is conducting research to improve the understanding of chronic beryllium disease (CBD) and beryllium-induced lung cancer. Initial animal studies examined beagle dogs that inhaled BeO calcined at either 500 or 1000{degrees}C. At similar lung burdens, the 500{degrees}C BeO induced more severe and extensive granulomatous pneumonia, lymphocytic infiltration into the lung, and positive Be-specific lymphocyte proliferative responses in vitro than the 1000{degrees}C BeO. However, the progressive nature of human CBD was not duplicated. More recently, Strains A/J and C3H/HeJ mice were exposed to Be metal by inhalation. This produced a marked granulomatous pneumonia, diffuse infiltrates, and multifocal aggregates of interstitial lymphocytes with a pronounced T helper component and pulmonary in situ lymphocyte proliferation. With respect to lung cancer, at a mean lung burden as low as 17 pg Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving {ge}1 year on study. Substantial tumor multiplicity was found, but K-ras and p53 gene mutations were virtually absent. In mice, however, a lung burden of approximately 60 {mu}g ({approximately}300 {mu}g Be/g lung) caused only a slight increase in crude lung tumor incidence and multiplicity over controls in strain A/J mice and no elevated incidence in strain C3H mice. Taken together, this research program constitutes a coordinated effort to understand beryllium-induced lung disease in experimental animal models. 47 refs., 1 fig., 3 tabs.

  2. [The prevention of allergic diseases with a hypoallergenic formula: a follow-up at 24 months. The preliminary results].

    PubMed

    de Seta, L; Siani, P; Cirillo, G; Di Gruttola, M; Cimaduomo, L; Coletta, S

    1994-01-01

    One hundred-eight infants from atopic families were admitted to the study. Each had at least one first-degree relative affected by asthma or rhinitis, conjunctivitis, eczema, cow's milk protein intolerance. All infants not breast fed were hypoallergenic formula. 46 infants were breast fed, 39 were bottle fed by the ordinary formula and 23 received the hypoallergenic one. No other food was introduced up to 6 months. Cow's milk proteins, egg, poultry and fish were introduced after 6 months. All infants were followed up to 24 months. Incidence of allergic diseases up to 24 months was not significantly different among the 3 groups. PMID:7971447

  3. [The prevention of allergic diseases with a hypoallergenic formula: a follow-up at 24 months. The preliminary results].

    PubMed

    de Seta, L; Siani, P; Cirillo, G; Di Gruttola, M; Cimaduomo, L; Coletta, S

    1994-01-01

    One hundred-eight infants from atopic families were admitted to the study. Each had at least one first-degree relative affected by asthma or rhinitis, conjunctivitis, eczema, cow's milk protein intolerance. All infants not breast fed were hypoallergenic formula. 46 infants were breast fed, 39 were bottle fed by the ordinary formula and 23 received the hypoallergenic one. No other food was introduced up to 6 months. Cow's milk proteins, egg, poultry and fish were introduced after 6 months. All infants were followed up to 24 months. Incidence of allergic diseases up to 24 months was not significantly different among the 3 groups.

  4. [Therapy of allergic rhinitis].

    PubMed

    Klimek, Ludger; Sperl, Annette

    2016-03-01

    If the avoidance of the provoking allergen is insufficient or not possible, medical treatment can be tried. Therapeutics of the first choice for the treatment of the seasonal and persistent allergic rhinitis are antihistamines and topical glucocorticoids. Chromones are less effective so they should only be used for adults with a special indication, for example during pregnancy. Beside the avoidance of the allergen the immunotherapy is the only causal treatment of allergic diseases. PMID:27120870

  5. [Therapeutic training and sports in chronic diseases of the lung].

    PubMed

    Podolsky, A; Haber, P

    1993-01-01

    Training is defined as systematic physical activity in order to improve the physical working capacity, which causes measurable morphological and functional changes in organs. Effects and the rules of applying aerobic endurance training in patients with chronic diseases of the lungs are dealt with. Training does not replace the normal medication, but is an additional therapeutic mean in order to regain physical working capacity, lost by chronic immobilization in the natural course of disease. Contraindications are acute diseases and exacerbations, but not a certain degree of the disease. Training does not improve the lung function, but the function of the other organs, the physical working capacity ist based on (circulation, musculature). This helps to use optimally the remaining reserves of lung function. Methods of aerobic endurance training are described, the definition of aims, performance diagnostic and the finding of the exact doses of training according to intensity, duration, frequency and the weekly netto training time. The training in different diseases of the lungs is discussed: In asthma bronchiale the prophylaxis of the exercise induced asthma and permitted and forbidden drugs for asthmatics according to the rules of international olympic committee. In chronic bronchitis with arterial hypoxemia, in restrictive lung diseases and in pulmonary hypertension. At last the way to prescribing training for patients with chronic pulmonary diseases is described as well as the advising of patients wishing to do sport by their own motivation or planning projects, for instance touristic ones, which require physical stress. PMID:8465532

  6. Anti-IgE monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases.

    PubMed

    D'Amato, Gennaro; Liccardi, Gennaro; Noschese, Paolo; Salzillo, Antonello; D'Amato, Maria; Cazzola, Mario

    2004-09-01

    Since the discovery of immunoglobulin E (IgE) antibodies thirty-six years ago, our understanding of the mechanisms of allergy has improved to such an extent that we can now better differentiate allergy from non-allergic hypersensitivity, and allergic/atopic from intrinsic/non-atopic bronchial asthma. IgE antibodies are crucial immune mediators of airway inflammation in allergic atopic asthma and IgE-mediated hypersensitivity reactions are the likely mechanisms of allergen-induced airway obstruction. In addition, IgE may cause chronic airway inflammation in asthma through effector cells activated via high-affinity (Fcepsilon RI) or low-affinity (Fcepsilon RII) IgE receptors. Therapeutic anti-IgE antibodies able to reduce free IgE levels and to block the binding of IgE to Fcepsilon RI without cross-linking IgE and triggering degranulation of IgE-sensitised cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (rhuMAb-E25; omalizumab) binds IgE at the same site as these antibodies bind Fcepsilon RI and Fcepsilon RII. As a consequence, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the Fcepsilon R1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma demonstrated that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted to be able to reduce asthma-related symptoms, to decrease corticosteroid use and to improve quality of life of asthmatic patients. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases (allergic rhinitis, allergic conjunctivitis, atopic dermatitis and food allergies), a favourable side-effect profile

  7. Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study

    PubMed Central

    2011-01-01

    Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and

  8. [GA(2)LEN (Global Allergy and Asthma European Network): European network of excellence for asthma and allergic diseases].

    PubMed

    Gjomarkaj, M; Pace, E; Canonica, G W; Bonini, S; Ricci, G; Burney, P; Zuberbier, T; Van Cauwenberge, P; Bousquet, J

    2009-12-01

    Allergic diseases represent some of the main health problems in Europe. These are increasing in prevalence, seriousness and social cost. The Global Allergy and Asthma European Network (GA(2)LEN), a network of excellence of the 6 degrees management program, was created in the 2005 with the aim to gather the European leader institutions of the research and clinical assistance fields, in order to guarantee the excellence and avoid the fragmentation of the energy spent in fighting allergy diseases in general. The GA(2)LEN has drawn a great advantage from the personal efforts of every single researcher who have proved their strong motivation in carrying on this "pan-European" model of collaboration. The network has been organized in order to increase the team work in scientific research projects in allergic and asthma disease field, making the GA(2)LEN the worldwide leader in this area. On these basis research projects have been carried on about which first data have been already published. The activities of the GA(2)LEN include in general the establishment of a lasting organization of the planning phase, the activity linked to every single project and to the improving on the existing projects, as well as the draft of new guidelines. This review reports the main achieved goals. PMID:20010485

  9. Airbag lung: an unusual case of sarcoid-like granulomatous lung disease after a rollover motor vehicle accident.

    PubMed

    Waring, Thomas P; Hegde, Poornima; Foley, Raymond J

    2014-05-01

    Sarcoid-like granulomatous lung disease (SLGLD) is a condition associated with the formation of noncaseating, nonnecrotizing granulomas. The final by-product of airbag deployment is alkaline silicates or glass. Silicates trapped and sequestered in the lung parenchyma are a potential mediator for immune system activation and development of sarcoid-like granulomatous lung disease.

  10. Specific and nonspecific obstructive lung disease in childhood: causes of changes in the prevalence of asthma.

    PubMed Central

    Platts-Mills, T A; Carter, M C; Heymann, P W

    2000-01-01

    Reversible airway obstruction in childhood includes two major groups of patients: those with recurrent wheezing following bronchiolitis in early childhood, and those with allergic asthma, which represents an increasingly large proportion of cases through the school years. Over the last 40 years of the 20th century, allergic asthma has increased in many countries and in relation to several different allergens. Although this increase has differed in magnitude in different countries and also in the social groups most affected, it has had several features in common. The increase generally started between 1960 and 1970, has been progressive since then, and has continued into the 1990s without a defined peak. Among children 5-18 years of age, the increase has predominantly been among allergic individuals. Theories about the causes of the increase in asthma have focused on two scenarios: a) that changes in houses combined with increased time spent indoors have increased exposure to relevant allergens, or b) that changes in diet, antibiotic use, immunizations, and the pattern of infections in childhood have led to a change in immune responsiveness such that a larger section of the population makes T(H)2, rather than T(H)1 responses including IgE antibodies to inhalant allergens. There are, however, problems with each of these theories and, in particular, none of the proposed changes can explain the progressive nature of the increase over 40 years. The fact that the change in asthma has much in common with epidemic increase in diseases such as Type II diabetes or obesity suggests that similar factors could be involved. Several lines of evidence are reviewed that suggest that the decline in physical activity of children, particularly those living in poverty in the United States, could have contributed to the rise in asthma. The hypothesis would be that the progressive loss of a lung-specific protective effect against wheezing has allowed allergic children to develop

  11. Specific and nonspecific obstructive lung disease in childhood: causes of changes in the prevalence of asthma.

    PubMed

    Platts-Mills, T A; Carter, M C; Heymann, P W

    2000-08-01

    Reversible airway obstruction in childhood includes two major groups of patients: those with recurrent wheezing following bronchiolitis in early childhood, and those with allergic asthma, which represents an increasingly large proportion of cases through the school years. Over the last 40 years of the 20th century, allergic asthma has increased in many countries and in relation to several different allergens. Although this increase has differed in magnitude in different countries and also in the social groups most affected, it has had several features in common. The increase generally started between 1960 and 1970, has been progressive since then, and has continued into the 1990s without a defined peak. Among children 5-18 years of age, the increase has predominantly been among allergic individuals. Theories about the causes of the increase in asthma have focused on two scenarios: a) that changes in houses combined with increased time spent indoors have increased exposure to relevant allergens, or b) that changes in diet, antibiotic use, immunizations, and the pattern of infections in childhood have led to a change in immune responsiveness such that a larger section of the population makes T(H)2, rather than T(H)1 responses including IgE antibodies to inhalant allergens. There are, however, problems with each of these theories and, in particular, none of the proposed changes can explain the progressive nature of the increase over 40 years. The fact that the change in asthma has much in common with epidemic increase in diseases such as Type II diabetes or obesity suggests that similar factors could be involved. Several lines of evidence are reviewed that suggest that the decline in physical activity of children, particularly those living in poverty in the United States, could have contributed to the rise in asthma. The hypothesis would be that the progressive loss of a lung-specific protective effect against wheezing has allowed allergic children to develop

  12. Dietary Enrichment with 20% Fish Oil Decreases Mucus Production and the Inflammatory Response in Mice with Ovalbumin-Induced Allergic Lung Inflammation

    PubMed Central

    Hall, Jean A.; Hartman, Jaye; Skinner, Monica M.; Schwindt, Adam R.; Fischer, Kay A.; Vorachek, William R.; Bobe, Gerd; Valentine, Beth A.

    2016-01-01

    The prevalence of asthma has increased in recent decades, which may be related to higher dietary intake of (n-6) polyunsaturated fatty acids (PUFA) and lower intake of (n-3) PUFA, e.g., those contained in fish oil. The objective of this study was to determine if dietary PUFA enrichment decreases mucus production or the inflammatory response associated with ovalbumin (OVA)-induced allergic lung inflammation. Mice (n = 10/group) were fed control, 20% fish oil, or 20% corn oil enriched diets for a total of 12 weeks. At 8 and 10 weeks, mice were given an intraperitoneal injection of saline (10 control-fed mice) or OVA (30 remaining mice). Once at 10 weeks and on 3 consecutive days during week 12, mice were challenged by nebulizing with saline or OVA. Mice were euthanized 24 hours after the last challenge and blood was collected for plasma FA analysis. Bronchoalveolar lavage (BAL) fluid was collected to determine cell composition and Th2-type cytokine (IL-4, IL-13) concentrations. Periodic acid-Schiff (PAS) + mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue were quantified using morphometric analysis. Relative abundance of mRNA for mucin (Muc4, Muc5ac, and Muc5b) and Th2-type cytokine (IL-4, IL-5, and IL-13) genes were compared with ß-actin by qPCR. Supplementation with either corn oil or fish oil effectively altered plasma FA profiles towards more (n-6) FA or (n-3) FA, respectively (P < 0.0001). Sensitization and challenge with OVA increased the proportion of neutrophils, lymphocytes, and eosinophils, and decreased the proportion of macrophages and concentrations of IL-13 in BAL fluid; increased the percentage of PAS+ mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue; and increased gene expression of mucins (Muc4, Muc5ac, and Muc5b) and Th2-type cytokines (IL-5 and IL-13) in lung tissue of control-fed mice. Dietary PUFA reversed the increase in PAS+ mucus-producing cells (P = 0.003). In addition, dietary

  13. Natural antibody repertoires: development and functional role in inhibiting allergic airway disease.

    PubMed

    Kearney, John F; Patel, Preeyam; Stefanov, Emily K; King, R Glenn

    2015-01-01

    In this review we discuss the effects of microbial exposure on the B cell repertoire. Neonatal exposure to conserved bacterial carbohydrates and phospholipids permanently reprograms the natural antibody repertoire directed toward these antigens by clonal expansion, alterations in clonal dominance, and increased serum antibody levels. These epitopes are present not only in bacterial cell walls, but also in common environmental allergens. Neonatal immunization with bacterial polysaccharide vaccines results in attenuated allergic airway responses to fungi-, house dust mite-, and cockroach-associated allergens in mouse models. The similarities between mouse and human natural antibody repertoires suggest that reduced microbial exposure in children may have the opposite effect, providing a potential mechanistic explanation for the hygiene hypothesis. We propose that understanding the effects of childhood infections on the natural antibody repertoire and the mechanisms of antibody-mediated immunoregulation observed in allergy models will lead to the development of prevention/interventional strategies for treatment of allergic asthma. PMID:25622195

  14. Strategies for Management of the Early Chronic Obstructive Lung Disease

    PubMed Central

    Lee, Jung Yeon; Rhee, Chin Kook; Jung, Ki Suck

    2016-01-01

    Lung function reportedly declines with age and that this decline is accelerated during disease progression. However, a recent study showed that the decline might peak in the mild and moderate stage. The prognosis of chronic obstructive pulmonary disease (COPD) can be improved if the disease is diagnosed in its early stages, prior to the peak of decline in lung function. This article reviews recent studies on early COPD and the possibility of applying the U.S. Preventive Services Task Force recommendation 2008 and 2015 for early detection of COPD in Korea. PMID:27433171

  15. Clinical Trials for Rare Lung Diseases: Lessons from Lymphangioleiomyomatosis

    PubMed Central

    McCormack, Francis X.

    2010-01-01

    Abstract Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive neoplasm that causes gradual but often life-threatening cystic destruction of the lung. Advances in our understanding of the molecular and cellular pathogenesis have LAM have identified a number of promising targets for testing in therapeutic trials. However, the design, prioritization, organization, and implementation of clinical trials in rare lung diseases poses unique challenges, including geographically disperse populations, sluggish enrollment, off- label drug use, burdensome regulations, and paucity of validated surrogate endpoints. PMID:20235889

  16. Lung function tests in neonates and infants with chronic lung disease: lung and chest-wall mechanics.

    PubMed

    Gappa, Monika; Pillow, J Jane; Allen, Julian; Mayer, Oscar; Stocks, Janet

    2006-04-01

    This is the fifth paper in a review series that summarizes available data and critically discusses the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). This review focuses on respiratory mechanics, including chest-wall and tissue mechanics, obtained in the intensive care setting and in infants during unassisted breathing. Following orientation of the reader to the subject area, we focused comments on areas of enquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically with respect to relevant methods, equipment and study design, limitations and strengths of different techniques, and availability and appropriateness of reference data. Recommendations to guide future investigations in this field are provided. Numerous different methods have been used to assess respiratory mechanics with the aims of describing pulmonary status in preterm infants and assessing the effect of therapeutic interventions such as surfactant treatment, antenatal or postnatal steroids, or bronchodilator treatment. Interpretation of many of these studies is limited because lung volume was not measured simultaneously. In addition, populations are not comparable, and the number of infants studied has generally been small. Nevertheless, results appear to support the pathophysiological concept that immaturity of the lung leads to impaired lung function, which may improve with growth and development, irrespective of the diagnosis of chronic lung disease. To fully understand the impact of immaturity on the developing lung, it is unlikely that a single parameter such as respiratory compliance or resistance will accurately describe underlying changes. Assessment of respiratory mechanics will have to be supplemented by assessment of lung volume and airway function. New methods such as the low-frequency forced oscillation technique, which

  17. [Fundamentals of chronic inflammatory lung diseases (asthma, COPD, fibrosis)].

    PubMed

    Roth, Michael

    2014-05-01

    Since three decades the prevalence of chronic inflammatory lung diseases (asthma, COPD, fibrosis) are worldwide increasing. In Switzerland about 5 % of the population develops asthma, while in other countries it affects up to 20 % (Maori: New Zealand). Today, asthma is the most frequent cause from absence from school and work, and significantly reduces life quality of the patients and their families. COPD, or the smoker's lung, is the 4th most frequent cause of death worldwide and in the Western society affects mainly cigarette smokers and ex-smokers, while in developing countries it is a diseases linked to open fire cocking with most patients being middle aged women. In both diseases only the symptoms can be controlled by muscle relaxing and anti-inflammatory drugs, but there is no cure available. The third chronic inflammatory lung disease is fibrosis which is increasing with the aging population. As indicated by the terminology "chronic inflammatory lung disease" it is widely assumed that the major cause of these diseases is chronic inflammation occurring in different segments of the lung. This hypothesis is now challenged as increasing evidence from clinical and experimental studies that suggest a much different pathogenesis. There is evidence that the inflammation may come second and tissue structural changes are already pre-set during embryogenesis and may become the major driver for the development of chronic inflammatory lung diseases later in life. The mechanism of this pre-disposition is largely unknown and the difficult to perform investigations have only started in recent years. This review aims to provide an overview of key studies published in the past 2 years on clinical and experimental research.

  18. VARIATIONS IN PEAK EXPIRATORY FLOW MEASUREMENTS ASSOCIATED TO AIR POLLUTION AND ALLERGIC SENSITIZATION IN CHILDREN IN SAO PAULO, BRAZIL

    PubMed Central

    de M Correia-Deur, Joya Emilie; Claudio, Luz; Imazawa, Alice Takimoto; Eluf-Neto, Jose

    2012-01-01

    Background In the last 20 years, there has been an increase in the incidence of allergic respiratory diseases worldwide and exposure to air pollution has been discussed as one of the factors associated with this increase. The objective of this study was to investigate the effects of air pollution on peak expiratory flow (PEF) and FEV1 in children with and without allergic sensitization. Methods Ninety-six children were followed from April to July, 2004 with spirometry measurements. They were tested for allergic sensitization (IgE, skin prick test, eosinophilia) and asked about allergic symptoms. Air pollution, temperature and relative humidity data were available. Results Decrements in PEF were observed with previous 24-h average exposure to air pollution, as well as with 3 to 10 day average exposure and were associated mainly with PM10, NO2 and O3. in all three categories of allergic sensitization. Even though allergic sensitized children tended to present larger decrements in the PEF measurements they were not statistically different from the non-allergic sensitized. Decrements in FEV1 were observed mainly with previous 24-h average exposure and 3-day moving average. Conclusions Decrements in PEF associated with air pollution were observed in children independent from their allergic sensitization status. Their daily exposure to air pollution can be responsible for a chronic inflammatory process that might impair their lung growth and later their lung function in adulthood. PMID:22544523

  19. Connective tissue diseases, multimorbidity and the ageing lung.

    PubMed

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients.

  20. Oxidative Stress and Therapeutic Development in Lung Diseases

    PubMed Central

    Villegas, Leah; Stidham, Timothy; Nozik-Grayck, Eva

    2016-01-01

    Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies. PMID:27019769

  1. [Pseudotumoral allergic bronchopulmonary aspergillosis].

    PubMed

    Otero González, I; Montero Martínez, C; Blanco Aparicio, M; Valiño López, P; Verea Hernando, H

    2000-06-01

    Allergic bronchopulmonary aspergillosis (ABPA) develops as the result of a hypersensitivity reaction to fungi of the genus Aspergillus. Clinical and radiological presentation can be atypical, requiring a high degree of suspicion on the part of the physician who treats such patients. We report the cases of two patients with APBA in whom the form of presentation--with few asthma symptoms, images showing lobar atelectasia and hilar adenopathy--led to an initial suspicion of lung cancer. PMID:10932345

  2. Profiling over 1500 lipids in induced lung sputum and the implications in studying lung diseases.

    PubMed

    t'Kindt, Ruben; Telenga, Eef D; Jorge, Lucie; Van Oosterhout, Antoon J M; Sandra, Pat; Ten Hacken, Nick H T; Sandra, Koen

    2015-01-01

    Induced lung sputum is a valuable matrix in the study of respiratory diseases. Although the methodology of sputum collection has evolved to a point where it is repeatable and responsive to inflammation, its use in molecular profiling studies is still limited. Here, an in-depth lipid profiling of induced lung sputum using high-resolution liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS) is described. An enormous complexity in lipid composition could be revealed. Over 1500 intact lipids, originating from 6 major lipid classes, have been accurately identified in 120 μL of induced sputum. By number and measured intensity, glycerophospholipids represent the largest lipid class, followed by sphingolipids, glycerolipids, fatty acyls, sterol lipids, and prenol lipids. Several prenol lipids, originating from tobacco, could be detected in the lung sputum of smokers. To illustrate the utility of the methodology in studying respiratory diseases, a comparative lipid screening was performed on lung sputum extracts in order to study the effect of Chronic Obstructive Pulmonary Disease (COPD) on the lung barrier lipidome. Results show that sphingolipid expression in induced sputum significantly differs between smokers with and without COPD.

  3. Allergic fungal otomastoiditis: a case report.

    PubMed

    Chen, Chiung-Ming; Chiang, Ching-Wen

    2013-04-01

    Allergic mucin is described as thick, peanut butter-like mucus impacted in the paranasal sinuses of patients with allergic fungal rhinosinusitis. The presence of allergic mucin in the middle ear has never been reported. We encountered a 65-year-old female with allergic mucin found impacted in her left middle ear and mastoid cavity during revised tympanoplasty surgery at our institute. Bilateral endoscopic sinus surgery performed 3 months later showed no evidence of fungal infection or allergic mucin in her paranasal sinuses. We report the case herein and propose the term allergic fungal otomastoiditis for this disease entity. PMID:22825725

  4. Differences in allergic inflammatory responses between urban PM2.5 and fine particle derived from desert-dust in murine lungs.

    PubMed

    He, Miao; Ichinose, Takamichi; Kobayashi, Makoto; Arashidani, Keiichi; Yoshida, Seiichi; Nishikawa, Masataka; Takano, Hirohisa; Sun, Guifan; Shibamoto, Takayuki

    2016-04-15

    The biological and chemical natures of materials adsorbed onto fine particulate matter (PM2.5) vary by origin and passage routes. The exacerbating effects of the two samples-urban PM2.5 (U-PM2.5) collected during the hazy weather in a Chinese city and fine particles (ASD-PM2.5) collected during Asian sand dust (ASD) storm event days in Japan-on murine lung eosinophilia were compared to clarify the role of toxic materials in PM2.5. The amounts of β-glucan and mineral components were higher in ASD-PM2.5 than in U-PM2.5. On the other hand, organic chemicals, including polycyclic aromatic hydrocarbons (PAHs), were higher in U-PM2.5 than in ASD-PM2.5. When BALB/c mice were intratracheally instilled with U-PM2.5 and ASD-PM2.5 (total 0.4 mg/mouse) with or without ovalbumin (OVA), various biological effects were observed, including enhancement of eosinophil recruitment induced by OVA in the submucosa of the airway, goblet cell proliferation in the bronchial epithelium, synergic increase of OVA-induced eosinophil-relevant cytokines and a chemokine in bronchoalveolar lavage fluid, and increase of serum OVA-specific IgG1 and IgE. Data demonstrate that U-PM2.5 and ASD-PM2.5 induced allergic inflammatory changes and caused lung pathology. U-PM2.5 and ASD-PM2.5 increased F4/80(+) CD11b(+) cells, indicating that an influx of inflammatory and exudative macrophages in lung tissue had occurred. The ratio of CD206 positive F4/80(+) CD11b(+) cells (M2 macrophages) in lung tissue was higher in the OVA+ASD-PM2.5 treated mice than in the OVA+U-PM2.5 treated mice. These results suggest that the lung eosinophilia exacerbated by both PM2.5 is due to activation of a Th2-associated immune response along with induced M2 macrophages and the exacerbating effect is greater in microbial element (β-glucan)-rich ASD-PM2.5 than in organic chemical-rich U-PM2.5. PMID:26917405

  5. Dietary prevention of allergic diseases in infants and small children. Part II. Evaluation of methods in allergy prevention studies and sensitization markers. Definitions and diagnostic criteria of allergic diseases.

    PubMed

    Muraro, Antonella; Dreborg, Sten; Halken, Susanne; Høst, Arne; Niggemann, Bodo; Aalberse, Rob; Arshad, Syed H; von Berg, Andrea; Carlsen, Kai-Håkon; Duschén, Karel; Eigenmann, Philippe; Hill, David; Jones, Catherine; Mellon, Michael; Oldeus, Göran; Oranje, Arnold; Pascual, Cristina; Prescott, Susan; Sampson, Hugh; Svartengren, Magnus; Vandenplas, Yvan; Wahn, Ulrich; Warner, Jill A; Warner, John O; Wickman, Magnus; Zeiger, Robert S

    2004-06-01

    The role of primary prevention of allergic disease has been a matter of debate for the last 40 years. In order to shed some light into this issue a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. The design of observational and interventional studies was evaluated with relevance to the important factors influencing outcome of studies on allergy development/prevention. in this analysis the statements of evidence as defined by WHO were applied. Best evidence of recommendations are those fulfilling the criteria for statements category 1 and 2 and grade of recommendations A and B as proposed by WHO. This survey include target group for dietary prevention and methods and diagnostic criteria of atopic dermatitis, asthma and food allergy for prevention studies.

  6. [Clinical study on development of nontuberculous mycobacterial lung disease].

    PubMed

    Kurashima, Atsuyuki

    2004-12-01

    DEVELOPEMENT OF MAC LUNG DISEASE: An increase of nodular bronchiectatic type of MAC lung disease becomes a problem among respiratory physician today. The reason is still unknown, but it seems to be globally recognized that this type of MAC disease is developing particularly in middle-aged woman. Some papers mentioned the existence of such type of MAC lung disease already early in the 70s, in Japan. Yamamoto described that 17 cases of middle lobe type lung disease out of 154 non-photochoromogen cases, and 76.5% were female, in 1970. Shimoide also pointed such type of 39 cases out of 240 MAC lung disease and 84.6% were female, in 1980. Prince reported MAC lung disease seen in old and middle age female of 21 cases including lethality example of 4 cases without a precedent disease in 1989. After his report, the international consensus of this peculiar type of MAC lung disease seems to be spread. In 1989, we compared 72 cases of nodular bronchiectatic type of MAC lung disease and 56 cases of diffuse panbronchiolitis (DPB) that was a most typical chronic airway disease at that time in Japan. The average age of disease onset of DPB group was 37.0 +/- 16.3 years old and that of MAC group was 54.5 +/- 16.3 years old. The percentage of female was 32% in DPB group and 87.5% in MAC group. It was highly possible that two groups belong different parent population. We could grasp that nodular bronchiectatic type of MAC lung disease patients is a unique group. We observed the serial films of 21 cases of nodular bronchiectatic MAC lung disease, and divide the progression of the disease to sequential 7 steps as Fig. 1. Small nodules progress to cavities in mean about 10 years. However, why is MAC which is opportunistic pathogen with weak virulence, able to form a lesion at unimpaired lung parenchyma? Is there really normal site? Why dose it start from lingula? Why is MAC seen a lot in woman? While it is extremely pathognomonic clinical picture, and, is an extremely interesting

  7. No Adjuvant Effect of Bacillus thuringiensis-Maize on Allergic Responses in Mice

    PubMed Central

    Dekan, Gerhard; Epstein, Michelle M.

    2014-01-01

    Genetically modified (GM) foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt)-maize (MON810) on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA)-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma. PMID:25084284

  8. Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation

    SciTech Connect

    Kato, Takuma; Tada-Oikawa, Saeko; Wang, Linan; Murata, Mariko; Kuribayashi, Kagemasa

    2013-11-15

    In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases. - Highlights: • Oral exposure to TBT exacerbates airway inflammation. • TBT induces oxidative stress in secondary lymphoid organs, but not in the lung. • TBT preferentially induces regulatory T cell apoptosis over non-Treg cells. • TBT does not enhance pre-existing airway inflammation in sensitized mice. • Chemicals in food contaminants

  9. Epigenetic targets for novel therapies of lung diseases

    PubMed Central

    Comer, Brian S.; Ba, Mariam; Singer, Cherie A.; Gerthoffer, William T.

    2014-01-01

    In spite of substantial advances in defining the immunobiology and function of structural cells in lung diseases there is still insufficient knowledge to develop fundamentally new classes of drugs to treat many lung diseases. For example, there is compelling need for new therapeutic approaches to address severe persistent asthma that is insensitive to inhaled corticosteroids. Although the prevalence of steroid-resistant asthma is 5–10%, severe asthmatics require a disproportionate level of health care spending and constitute a majority of fatal asthma episodes. None of the established drug therapies including long-acting beta agonists or inhaled corticosteroids reverse established airway remodeling. Obstructive airways remodeling in patients with chronic obstructive pulmonary disease (COPD), restrictive remodeling in idiopathic pulmonary fibrosis (IPF) and occlusive vascular remodeling in pulmonary hypertension are similarly unresponsive to current drug therapy. Therefore, drugs are needed to achieve long-acting suppression and reversal of pathological airway and vascular remodeling. Novel drug classes are emerging from advances in epigenetics. Novel mechanisms are emerging by which cells adapt to environmental cues, which include changes in DNA methylation, histone modifications and regulation of transcription and translation by noncoding RNAs. In this review we will summarize current epigenetic approaches being applied to preclinical drug development addressing important therapeutic challenges in lung diseases. These challenges are being addressed by advances in lung delivery of oligonucleotides and small molecules that modify the histone code, DNA methylation patterns and miRNA function. PMID:25448041

  10. Occupational lung diseases and the mining industry in Mongolia

    SciTech Connect

    Lkhasuren, O.; Takahashi, K.; Dash-Onolt, L.

    2007-04-15

    Mining production has accounted for around 50% of the gross industrial product in Mongolia since 1998. Dust-induced chronic bronchitis and pneumoconiosis currently account for the largest relative share (67.8%) of occupational diseases in Mongolia, and cases are increasing annually. In 1967-2004, medically diagnosed cases of occupational diseases in Mongolia numbered 7,600. Of these, 5,154 were confirmed cases of dust-induced chronic bronchitis and pneumoconiosis. Lung diseases and other mining-sector health risks pose major challenges for Mongolia. Gold and coal mines, both formal and informal, contribute significantly to economic growth, but the prevalence of occupational lung diseases is high and access to health care is limited. Rapid implementation of an effective national program of silicosis elimination and pneumoconiosis reduction is critical to ensure the health and safety of workers in this important sector of the Mongolian economy.

  11. Pulmonary functional magnetic resonance imaging for paediatric lung disease.

    PubMed

    Kirby, Miranda; Coxson, Harvey O; Parraga, Grace

    2013-09-01

    A better understanding of the anatomic structure and physiological function of the lung is fundamental to understanding the pathogenesis of pulmonary disease and how to design and deliver better treatments and measure response to intervention. Magnetic resonance imaging (MRI) with the hyperpolarised noble gases helium-3 ((3)He) and xenon-129 ((129)Xe) provides both structural and functional pulmonary measurements, and because it does not require the use of x-rays or other ionising radiation, offers the potential for intensive serial and longitudinal studies in paediatric patients. These facts are particularly important in the evaluation of chronic lung diseases such as asthma and cystic fibrosis- both of which can be considered paediatric respiratory diseases with unmet therapy needs. This review discusses MRI-based imaging methods with a focus on hyperpolarised gas MRI. We also discuss the strengths and limitations as well as the future work required for clinical translation towards paediatric respiratory disease. PMID:23522599

  12. Allergic Fungal Rhinosinusitis.

    PubMed

    Hoyt, Alice E W; Borish, Larry; Gurrola, José; Payne, Spencer

    2016-01-01

    This article reviews the history of allergic fungal rhinosinusitis and the clinical, pathologic, and radiographic criteria necessary to establish its diagnosis and differentiate this disease from other types of chronic rhinosinusitis. Allergic fungal rhinosinusitis is a noninvasive fungal form of sinus inflammation characterized by an often times unilateral, expansile process in which the typical allergic "peanut-butter-like" mucin contributes to the formation of nasal polyps, hyposmia/anosmia, and structural changes of the face. IgE sensitization to fungi is a necessary, but not sufficient, pathophysiologic component of the disease process that is also defined by microscopic visualization of mucin-containing fungus and characteristic radiological imaging. This article expounds on these details and others including the key clinical and scientific distinctions of this diagnosis, the pathophysiologic mechanisms beyond IgE-mediated hypersensitivity that must be at play, and areas of current and future research. PMID:27393774

  13. Lung clearance index in the assessment of airways disease.

    PubMed

    Horsley, Alex

    2009-06-01

    In the last few years there has been a growing interest in lung clearance index (LCI), a measure of lung physiology derived from multiple breath washout tests. This resurgence of interest was initially driven by the recognition that such assessments were capable of detecting early airways disease in children, and are more sensitive and easier to perform in this population than conventional lung function tests [Aurora P, Kozlowska W, Stocks J. Gas mixing efficiency from birth to adulthood measured by multiple-breath washout. Respir Physiol Neurobiol, 2005;148(1-2):125-39]. With an appreciation of the importance of earlier identification of airways dysfunction, and prevention of irreversible structural airway changes, methods of following airways disease in these "silent years" are especially important. LCI has now been reported in studies involving all age groups, from infants to adults [Lum S, Gustafsson P, Ljungberg H, Hulskamp G, Bush A, Carr SB, et al. Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests. Thorax, 2007;62(4):341-7; Horsley AR, Gustafsson PM, Macleod K, Saunders CJ, Greening AP, Porteous D, et al. Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. Thorax, 2008;63:135-40], and has a narrow range of normal over this wide age range, making it especially suitable for long-term follow-up studies. In cystic fibrosis (CF) particularly, there is a pressing need for sensitive and repeatable clinical endpoints for therapeutic interventions [Rosenfeld M. An overview of endpoints for cystic fibrosis clinical trials: one size does not fit all. Proc Am Thorac Soc, 2007;4(4):299-301], and LCI has been proposed as an outcome measure in future CF gene therapy studies [Davies JC, Cunningham S, Alton EW, Innes JA. Lung clearance index in CF: a sensitive marker of lung disease severity. Thorax, 2008;63(2):96-7]. This review will consider how LCI is

  14. Interstitial lung disease induced by alectinib (CH5424802/RO5424802).

    PubMed

    Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi

    2015-02-01

    A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile.

  15. Evidence for clinical safety, efficacy, and parent and physician perceptions of levocetirizine for the treatment of children with allergic disease.

    PubMed

    Pampura, A N; Papadopoulos, N G; Spičák, V; Kurzawa, R

    2011-01-01

    Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are highly burdensome diseases, which are increasing in prevalence, especially in the paediatric population. Despite the availability of a large number of medications for treatment of AR and CIU, their use in children has primarily been based on data obtained from a limited number of clinical trials in children and/or testing in adults. The H(1)-antihistamines have traditionally been used as first-line treatment for the relief of both AR and CIU symptoms in children. The first-generation H(1)-antihistamines are associated with marked adverse effects such as sedation, sleepiness/drowsiness as well as difficulties in learning and cognitive processing; thus, they are recommended for limited or discontinued use in children with AR or CIU. In contrast, second-generation H(1)-antihistamines are more adapted for the use in children with AR and CIU due to better safety profiles. However, only a limited number of trials with these agents have been conducted and generally, data from well-designed trials in children are lacking. Levocetirizine is one of the most extensively investigated H(1)-antihistamines for its pharmacologic properties, safety, efficacy as well as overall global satisfaction in children aged 2-12 years. Levocetirizine is the only H(1)-antihistamine launched in the 21st century shown to lack clinically relevant adverse effects on physical and psychomotor development or routine laboratory tests over a long-term period of 18 months in 1- to 3-year-old children predisposed to development of allergic disease. Available data suggest that levocetirizine is a suitable treatment option for AR and CIU in children aged 6 months to 12 years.

  16. Prevalence of asthma and allergic diseases in primary school children in Edirne, Turkey, two surveys 10 years apart.

    PubMed

    Selcuk, Ziya Toros; Demir, Ahmet Ugur; Tabakoglu, Erhan; Caglar, Tuncay

    2010-06-01

    To assess change in prevalence and risk factors of asthma and allergic diseases among primary school children in rural and urban parts of Edirne, Turkey, a series of cross-sectional studies were conducted in 1994 and 2004. A questionnaire was administered to the parents of primary school children aged 7-12, in urban and rural parts of Edirne, Turkey (5412 in 1994 and 5735 in 2004). Response rates in 1994 and 2004 were 84% and 82.5%, respectively. There were significant differences between the age distribution, urban habitation (1994: 70.1%, 2004: 75.8%, p < 0.001), passive smoking (1994: 74.7%, 2004: 60.0%, p < 0.001), and family atopy (1994: 12.7%, 2004: 18.2%, p < 0.001) between the two surveys. Current prevalence of asthma and wheeze increased in the 2004 when compared to 1994 in both rural and urban regions (current asthma for rural and urban regions, 5.2% and 5.8% in 1994; 8.6% and 12.1% in 2004, respectively). Female-to-male ratio of current asthma increased from 0.7 in 1994 to 0.9 in 2004. Comparison of the risk factors in the two surveys suggested urban habitation and factors other than family atopy, passive smoking and no breast feeding as possible contributors for the increasing asthma and wheeze. Prevalence of asthma and allergic diseases increased among school children in Edirne, Turkey from 1994 to 2004. Life style changes and urbanization could be related to this increasing trend.

  17. Allergic Reactions

    MedlinePlus

    ... immune system identifies pollen as an invader or allergen. Your immune system overreacts by producing antibodies called ... IgE has specific "radar" for each type of allergen. That's why some people are only allergic to ...

  18. [Cytokines and allergic response].

    PubMed

    Guenounou, M

    1998-01-01

    Allergic reactions are under the control of several events that occur sequentially following allergen exposure, recognition by the immune system, IgE production and their interaction with effector cells bearing Fc epsilon receptors. The lymphocyte activation in response to allergens determines the intensity and the nature of the immune response. Cytokines produced by T (and non-T) cells are involved in the polarized development of the specific immune response. In particular, type 1 and type 2 cytokines are responsible for the control of the different steps during allergic reactions. Th2 cytokines and particularly IL4 are responsible for switching the immunoglobulin synthesis by B cells to IgE production. They also play a key role in the activation of effector cells that occurs following allergen interaction with fixed specific IgE and participate to the local inflammatory reaction. Cytokine profile determination appears to represent a helpful laboratory parameter in the understanding of the mechanisms underlying allergic diseases. The development of new technological tools may allow the use of cell activation parameters, and cytokine profiles determination in clinical biology. This review aims to analyze the involvement of the cytokine network in the mechanisms leading to IgE production and the involvement of cytokines in effector mechanisms of allergic reactions. It also analyses the potential use of cytokine profile determination for diagnosis purpose and survey of immune desensitization of allergic diseases.

  19. The clinical features of migraine as a manifestation of allergic disease.

    PubMed Central

    Wilson, C. W.; Kirker, J. G.; Warnes, H.; O'Malley, M.

    1980-01-01

    Patients with a clinical history of migraine were evaluated psychiatrically, and by electroencephalography. They were challenged with food antigens by skin-prick test, and abdominal symptoms were evaluated following oral ingestion of food allergens. A significant correlation was found between challenge with specific food allergens and the development of migraine headaches, the appearance of abdominal symptoms and the occurrence of positive skin reactions. Psychiatric abnormalities and EEG alterations were associated with the occurrence of headaches and allergic clinical features. It is suggested that the clinical features of migraine can be explained as a result of release of chemical mediators following antigen-antibody reactions in the brain and other tissues where specific antibodies are localized. The continuous ingestion of the responsible food allergens would account for the raised tissue concentrations of noradrenaline, histamine and other mediators to which the clinical features of migraine are attributed. PMID:7465468

  20. Extrinsic and intrinsic asthma: influence of classification on family history of asthma and allergic disease.

    PubMed

    Sibbald, B

    1980-05-01

    The distributions of asthma, hay fever and eczema were examined in the first degree relatives of 516 asthmatics grouped according to atopic status, history of hay fever/eczema and history of asthma provoked by pollens, dust or animals. The prevalences of both asthma and eczema in relatives were strongly correlated with the presence of hay fever/eczema in probands and to a lesser extent with their atopic status. The prevalence of hay fever in relatives was strongly correlated with both the presence of hay fever/eczema and the degree of atopy in probands. In contrast, allergic provocation of asthma in probands did not influence the prevalences of asthma, hay fever or eczema. These findings are consistent with the hypothesis that there is an increased risk of asthma in relatives of atopic asthmatics which may arise from the enhanced susceptibility to asthma of individuals who inherit both a predisposition to asthma and a predisposition to atopy.

  1. Measurement of serum immunoglobulin E (IgE) specific for house dust mite antigens in normal cats and cats with allergic skin disease.

    PubMed

    Taglinger, K; Helps, C R; Day, M J; Foster, A P

    2005-05-01

    The purpose of this study was to determine whether cats with allergic skin disease have significant concentrations of serum Immunoglobulin E (IgE) specific for antigens derived from the house dust mites (HDM) Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP). Enzyme-linked immunosorbent assays (ELISA) were developed for this purpose. Binding of serum allergen-specific IgE was detected via the use of biotinylated Fc-epsilon receptor alpha chain protein (FcvarepsilonRIalpha). Following optimisation of the assay, serum samples from 59 cats with allergic skin disease and 54 clinically normal cats were screened. Results were expressed as ELISA units per ml (EU/ml) compared to a standard curve. Serological findings were correlated with the clinical presentation of affected cats. Cats with symptoms of feline allergic skin disease were grouped as follows: self-induced alopecia without lesions (group 1), papulocrusting dermatitis (group 2), eosinophilic granuloma complex (group 3), papular/ulcerative dermatitis of head and neck/facial dermatitis (group 4), and a combination of symptoms (group 5). Control normal cats comprised the final group (group 6). The Kruskal-Wallis test was used for statistical analysis. There was no significant difference between groups for DF- and DP-specific IgE concentrations with a p-value of 0.875 and 0.705, respectively. Although the FcvarepsilonRIalpha-based ELISA was able to detect house dust mite-specific feline IgE, the presence of this allergen-specific IgE correlates poorly with the presence of clinical manifestations of allergic skin disease. The results of this study question the clinical relevance of house dust mite-specific IgE in feline allergic skin disease.

  2. Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency.

    PubMed

    Fuchs, Susanne I; Schwerk, Nicolaus; Pittschieler, Klaus; Ahrens, Frank; Baden, Winfried; Bals, Robert; Fähndrich, Sebastian; Gleiber, Wolfgang; Griese, Matthias; Hülskamp, Georg; Köhnlein, Thomas; Reckling, Ludmilla; Rietschel, Ernst; Staab, Doris; Gappa, Monika

    2016-07-01

    Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ. PMID:27296827

  3. Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35.

    PubMed

    Moldaver, D M; Bharhani, M S; Wattie, J N; Ellis, R; Neighbour, H; Lloyd, C M; Inman, M D; Larché, M

    2014-03-01

    In the present study, we show therapeutic amelioration of established ovalbumin (OVA)-induced allergic airway disease following house dust mite (HDM) peptide therapy. Mice were sensitized and challenged with OVA and HDM protein extract (Dermatophagoides species) to induce dual allergen sensitization and allergic airway disease. Treatment of allergic mice with peptides derived from the major allergen Der p 1 suppressed OVA-induced airway hyperresponsiveness, tissue eosinophilia, and goblet cell hyperplasia upon rechallenge with allergen. Peptide treatment also suppressed OVA-specific T-cell proliferation. Resolution of airway pathophysiology was associated with a reduction in recruitment, proliferation, and effector function of T(H)2 cells and decreased interleukin (IL)-17⁺ T cells. Furthermore, peptide immunotherapy induced the regulatory cytokine IL-10 and increased the proportion of Fox p3⁺ cells among those expressing IL-10. Tolerance to OVA was not associated with increased IL-35. In conclusion, our results provide in vivo evidence for the creation of a tolerogenic environment following HDM peptide immunotherapy, leading to the therapeutic amelioration of established OVA-induced allergic airway disease.

  4. Lung function, breathing pattern, and gas exchange in interstitial lung disease.

    PubMed Central

    Javaheri, S; Sicilian, L

    1992-01-01

    BACKGROUND: The aim of this study was to determine the relation between the severity of abnormalities in ventilatory function tests and tidal breathing pattern and gas exchange indices in interstitial lung disease. METHODS: Pulmonary function, ventilation, carbon dioxide production, oxygen consumption, arterial blood gas tensions, and pH were measured during resting steady state conditions in 60 patients with proved interstitial lung disease. Patients were categorised by forced vital capacity (FVC) (percentage of predicted values) as having a mild, moderate, or severe restrictive defect with means (SD) of 71% (4%), 57% (4%), and 41% (7%) of predicted values, respectively. RESULTS: FVC varied from 29% to 79% of predicted values and from 0.99 l to 4.32 l. The two measurements of FVC correlated strongly with most static lung volumes and with transfer factor for carbon monoxide. Mean respiratory rates (per minute) and tidal volumes (ml) were 17 (4) and 484 (131), 20 (4) and 460 (139), and 23 (5) and 377 (109) in mild, moderate, and severe restrictive defects, respectively. FVC correlated negatively with respiratory rate and positively with tidal volume. Arterial carbon dioxide tension ranged from 30 to 49 mm Hg; only two patients were hypercapnic. Mean arterial oxygen tensions were not significantly different among the three groups, and there were no significant correlations between forced expiratory volume in one second or FVC and arterial carbon dioxide tension or carbon dioxide production. CONCLUSION: Low values of FVC were associated with increased respiratory rate and decreased tidal volume; this pattern of breathing mimics external elastic loading, suggesting that mechanoreceptors may contribute to the rapid and shallow pattern of breathing in interstitial lung disease. Hypercapnia seems to be rare in interstitial lung disease even when functional impairment is severe and tidal volume is small. The increased respiratory rate is important in maintaining adequate

  5. Small airways involvement in coal mine dust lung disease.

    PubMed

    Long, Joshua; Stansbury, Robert C; Petsonk, Edward L

    2015-06-01

    Inhalation of coal mine dust results in a spectrum of symptoms, dysfunction, and pathological changes in the respiratory tract that collectively have been labeled coal mine dust lung disease. Recent reports from periodic health surveillance among underground and surface coal miners in the United States have demonstrated an increasing prevalence and severity of dust diseases, and have also documented that some miners experience rapid disease progression. The coal macule is an inflammatory lesion associated with deposited dust, and occurs in the region of the most distal conducting airways and proximal respiratory bronchioles. Inflammatory changes in the small airways have long been recognized as the signature lung pathology among coal miners. Human and laboratory studies have suggested oxidant injury, and increased recruitment and activity of macrophages play important roles in dust-induced lung injury. However, the functional importance of the small airway changes was debated for many years. We reviewed published literature that documents a pervasive occurrence of both physiologic and structural abnormalities in small airways among coal miners and other workers exposed to airborne particulates. There is increasing evidence supporting an important association of abnormalities in the small peripheral airways with the development of respiratory symptoms, deficits in spirometry values, and accelerated declines in ventilatory lung function. Pathologic changes associated with mineral dust deposition in the small airways may be of particular importance in contemporary miners with rapidly progressive respiratory impairment.

  6. Probiotics in the management of lung diseases.

    PubMed

    Mortaz, Esmaeil; Adcock, Ian M; Folkerts, Gert; Barnes, Peter J; Paul Vos, Arjan; Garssen, Johan

    2013-01-01

    The physiology and pathology of the respiratory and gastrointestinal tracts are closely related. This similarity between the two organs may underlie why dysfunction in one organ may induce illness in the other. For example, smoking is a major risk factor for COPD and IBD and increases the risk of developing Crohn's disease. Probiotics have been defined as "live microorganisms which, when administered in adequate amounts, confer health benefits on the host." In model systems probiotics regulate innate and inflammatory immune responses. Commonly used probiotics include lactic acid bacteria, particularly Lactobacillus, Bifidobacterium, and Saccharomyces, and these are often used as dietary supplements to provide a health benefit in gastrointestinal diseases including infections, inflammatory bowel disease, and colon cancer. In this respect, probiotics probably act as immunomodulatory agents and activators of host defence pathways which suggest that they could influence disease severity and incidence at sites distal to the gut. There is increasing evidence that orally delivered probiotics are able to regulate immune responses in the respiratory system. This review provides an overview of the possible role of probiotics and their mechanisms of action in the prevention and treatment of respiratory diseases.

  7. Probiotics in the management of lung diseases.

    PubMed

    Mortaz, Esmaeil; Adcock, Ian M; Folkerts, Gert; Barnes, Peter J; Paul Vos, Arjan; Garssen, Johan

    2013-01-01

    The physiology and pathology of the respiratory and gastrointestinal tracts are closely related. This similarity between the two organs may underlie why dysfunction in one organ may induce illness in the other. For example, smoking is a major risk factor for COPD and IBD and increases the risk of developing Crohn's disease. Probiotics have been defined as "live microorganisms which, when administered in adequate amounts, confer health benefits on the host." In model systems probiotics regulate innate and inflammatory immune responses. Commonly used probiotics include lactic acid bacteria, particularly Lactobacillus, Bifidobacterium, and Saccharomyces, and these are often used as dietary supplements to provide a health benefit in gastrointestinal diseases including infections, inflammatory bowel disease, and colon cancer. In this respect, probiotics probably act as immunomodulatory agents and activators of host defence pathways which suggest that they could influence disease severity and incidence at sites distal to the gut. There is increasing evidence that orally delivered probiotics are able to regulate immune responses in the respiratory system. This review provides an overview of the possible role of probiotics and their mechanisms of action in the prevention and treatment of respiratory diseases. PMID:23737654

  8. Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

    PubMed

    Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

    2015-01-01

    The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

  9. Detection of interstitial lung disease in PA chest radiographs

    NASA Astrophysics Data System (ADS)

    Loog, Marco; van Ginneken, Bram; Nielsen, Mads

    2004-05-01

    A computer-aided diagnosis scheme for the detection of interstitial disease in standard digital posteroanterior (PA) chest radiographs is presented. The detection technique is supervised-manually labelled data should be provided for training the algorithm-and fully automatic, and can be used as part of a computerized analysis scheme for X-ray lung images. Prior to the detection, a segmentation should be performed which delineates the lung field boundaries. Subsequently, a quadratic decision rule is employed for every pixel within the lung fields to associate with each pixel a probabilistic measure indicating interstitial disease. The locally obtained per-pixel probabilities are fused to a single global probability indicating to what extent there is interstitial disease present in the image. Finally, a threshold on this quantity classifies the image as containing interstitial disease or not. The probability combination scheme presented utilizes the quantiles of the local posterior probabilities to fuse the local probability into a global one. Using this nonparametric technique, reasonable results are obtained on the interstitial disease detection task. The area under the receiver operating characteristic equals 0.92 for the optimal setting.

  10. Processing of CT images for analysis of diffuse lung disease in the lung tissue research consortium

    NASA Astrophysics Data System (ADS)

    Karwoski, Ronald A.; Bartholmai, Brian; Zavaletta, Vanessa A.; Holmes, David; Robb, Richard A.

    2008-03-01

    The goal of Lung Tissue Resource Consortium (LTRC) is to improve the management of diffuse lung diseases through a better understanding of the biology of Chronic Obstructive Pulmonary Disease (COPD) and fibrotic interstitial lung disease (ILD) including Idiopathic Pulmonary Fibrosis (IPF). Participants are subjected to a battery of tests including tissue biopsies, physiologic testing, clinical history reporting, and CT scanning of the chest. The LTRC is a repository from which investigators can request tissue specimens and test results as well as semi-quantitative radiology reports, pathology reports, and automated quantitative image analysis results from the CT scan data performed by the LTRC core laboratories. The LTRC Radiology Core Laboratory (RCL), in conjunction with the Biomedical Imaging Resource (BIR), has developed novel processing methods for comprehensive characterization of pulmonary processes on volumetric high-resolution CT scans to quantify how these diseases manifest in radiographic images. Specifically, the RCL has implemented a semi-automated method for segmenting the anatomical regions of the lungs and airways. In these anatomic regions, automated quantification of pathologic features of disease including emphysema volumes and tissue classification are performed using both threshold techniques and advanced texture measures to determine the extent and location of emphysema, ground glass opacities, "honeycombing" (HC) and "irregular linear" or "reticular" pulmonary infiltrates and normal lung. Wall thickness measurements of the trachea, and its branches to the 3 rd and limited 4 th order are also computed. The methods for processing, segmentation and quantification are described. The results are reviewed and verified by an expert radiologist following processing and stored in the public LTRC database for use by pulmonary researchers. To date, over 1200 CT scans have been processed by the RCL and the LTRC project is on target for recruitment of the

  11. Respiratory and allergic diseases: from upper respiratory tract infections to asthma.

    PubMed

    Jaber, Raja

    2002-06-01

    Patients with asthma and allergic rhinitis may benefit from hydration and a diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3 fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds), onions, and fruits and vegetables (at least five servings a day). Physicians may need to be more cautious when prescribing antibiotics to children in their first year of life when they are born to families with a history of atopy. More research is needed to establish whether supplementation with probiotics (lactobacillus and bifidobacterium) during the first year of life or after antibiotic use decreases the risk of developing asthma and allergic rhinitis. Despite a theoretic basis for the use of vitamin C supplements in asthmatic patients, the evidence is still equivocal, and long-term studies are needed. The evidence is stronger for exercise-induced asthma, in which the use of vitamin C supplementation at a dosage of 1 to 2 g per day may be helpful. It is also possible that fish oil supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day, also may be helpful to some patients with asthma. Long-term studies of fish oil and vitamin C are needed for more definite answers. For the patient interested in incorporating nutritional approaches, vitamin C and fish oils have a safe profile. However, aspirin-sensitive individuals should avoid fish oils, and red blood cell magnesium levels may help in making the decision whether to use additional magnesium supplements. Combination herbal formulas should be used in the treatment of asthma with medical supervision and in collaboration with an experienced herbalist or practitioner of TCM. Safe herbs, such as Boswellia and gingko, may be used singly as adjuncts to a comprehensive plan of care if the patient and practitioner have an interest in trying them while staying alert for drug-herb interactions. No data on the long-term use of these single herbs in asthma exist. For the motivated

  12. Proposed national strategies for the prevention of leading work-related diseases and injuries. Occupational lung diseases

    SciTech Connect

    Not Available

    1986-01-01

    The document summarizes what actions need to be taken to prevent occupational lung diseases. The United States Public Health Service has established the following national objectives for the prevention of occupational lung diseases: 'By 1990, among workers newly exposed after 1985, there should be virtually no new cases of four preventable occupational lung diseases--asbestosis, byssinosis, silicosis, and coal workers' pneumoconiosis.' These four chronic lung diseases will be used as examples in the prevention strategy. To the extent that they are typical of most occupational lung diseases, potential prevention methods available for their control are not unique.

  13. Building a reference multimedia database for interstitial lung diseases.

    PubMed

    Depeursinge, Adrien; Vargas, Alejandro; Platon, Alexandra; Geissbuhler, Antoine; Poletti, Pierre-Alexandre; Müller, Henning

    2012-04-01

    This paper describes the methodology used to create a multimedia collection of cases with interstitial lung diseases (ILDs) at the University Hospitals of Geneva. The dataset contains high-resolution computed tomography (HRCT) image series with three-dimensional annotated regions of pathological lung tissue along with clinical parameters from patients with pathologically proven diagnoses of ILDs. The motivations for this work is to palliate the lack of publicly available collections of ILD cases to serve as a basis for the development and evaluation of image-based computerized diagnostic aid. After 38 months of data collection, the library contains 128 patients affected with one of the 13 histological diagnoses of ILDs, 108 image series with more than 41l of annotated lung tissue patterns as well as a comprehensive set of 99 clinical parameters related to ILDs. The database is available for research on request and after signature of a license agreement.

  14. Combination therapy with relaxin and methylprednisolone augments the effects of either treatment alone in inhibiting subepithelial fibrosis in an experimental model of allergic airways disease.

    PubMed

    Royce, Simon G; Sedjahtera, Amelia; Samuel, Chrishan S; Tang, Mimi L K

    2013-01-01

    Although CSs (corticosteroids) demonstrate potent effects in the control of airway inflammation in asthma, many patients continue to experience symptoms and AHR (airway hyper-responsiveness) despite optimal treatment with these agents, probably due to progressive airway remodelling. Identifying novel therapies that can target airway remodelling and/or airway reactivity may improve symptom control in these patients. We have demonstrated previously that the anti-fibrotic hormone RLN (relaxin) can reverse airway remodelling (epithelial thickening and subepithelial fibrosis) and AHR in a murine model of AAD (allergic airways disease). In the present study, we compared the effects of RLN with a CS (methylprednisolone) on airway remodelling and AHR when administered independently or in combination in the mouse AAD model. Female mice at 6-8 weeks of age were sensitized and challenged to OVA (ovalbumin) over a 9-week period and treated with methylprednisolone, RLN, a combination of both treatments or vehicle controls. Methylprednisolone was administered intraperitoneally on the same day as nebulization for 6 weeks, whereas recombinant human RLN-2 was administered via subcutaneously implanted osmotic mini-pumps from weeks 9-11. RLN or methylprednisolone alone were both able to significantly decrease subepithelial thickness and total lung collagen deposition; whereas RLN but not methylprednisolone significantly decreased epithelial thickness and AHR. Additionally, combination therapy with CS and RLN more effectively reduced subepithelial collagen thickness than either therapy alone. These findings demonstrate that RLN can modulate a broader range of airway remodelling changes and AHR than methylprednisolone and the combination of both treatments offers enhanced control of subepithelial fibrosis. PMID:22817662

  15. Effects of fiber characteristics on lung deposition, retention, and disease.

    PubMed Central

    Lippmann, M

    1990-01-01

    There is abundant epidemiologic evidence that asbestos fibers can cause lung fibrosis (asbestosis), bronchial cancer, and mesothelioma in humans, as well as limited evidence for such effects in workers exposed to slag and rockwool fibers. Epidemiological evidence for human disease from inhalation exposures to conventional fibrous glass is negative. While health concerns based on the morphological and toxicological similarities between man-made fibers and asbestos are warranted, it is important to note that most of the toxicological evidence for glass fiber toxicity in laboratory animals is based on nonphysiological exposures such as intratracheal instillation or intraperitoneal injection of fiber suspensions. Man-made fibers have produced lung fibrosis and mesotheliomas in such tests, albeit at much lower yields than asbestos. For all durable mineral fibers, critical length limits must be exceeded to warrant concern about chronic toxicity; i.e., 2 microns for asbestosis, 5 microns for mesothelioma, and 10 microns for lung cancer. Fiber width must be less than 0.1 microns for mesothelioma, and larger than this limit for asbestosis and lung cancer. The human health risks for most fibrous glass products are either low or negligible for a variety of reasons. First, most commercial fibrous glass products have mean fiber diameters of approximately 7.5 microns, which results in mean aero-dynamic diameters approximately 22 microns. Thus, most glass fibers, even if dispersed into the air, do not penetrate into the lung to any great extent. Second, the small fraction of smaller diameter fibers that do penetrate into the lungs are not persistent within the lungs for most fibrous glass products due to mechanical breakage into shorter lengths and overall dissolution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2272328

  16. β2-agonist therapy in lung disease.

    PubMed

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  17. AN EMERGING ROLE FOR THE LIPID MEDIATOR SPHINGOSINE-1-PHOSPHATE IN MAST CELL EFFECTOR FUNCTION AND ALLERGIC DISEASE*

    PubMed Central

    Olivera, Ana; Rivera, Juan

    2011-01-01

    Sphingosine-1-phosphate (S1P) plays important roles regulating functions of diverse biological systems, including the immune system. S1P affects immune cell function mostly by acting through its receptors at the cell membrane but it can also induce S1P receptor-independent responses in the cells where it is generated. S1P produced in allergically stimulated mast cells mediates degranulation, cytokine and lipid mediator production, and migration of mast cells towards antigen by mechanisms that are both S1P receptor-dependent and independent. Even in the absence of an antigen challenge, the differentiation and responsiveness of mast cells can be affected by chronic exposure to elevated S1P from a non-mast cell source, which may occur under pathophysiological conditions, potentially leading to the hyper-responsiveness of mast cells. The role of S1P extends beyond the regulation of the function of mast cells to the regulation of the surrounding or distal environment. S1P is exported out of antigen-stimulated mast cells and into the extracellular space and the resulting S1P gradient within the tissue may influence diverse surrounding tissue cells and several aspects of the allergic disease, such as inflammation or tissue remodeling. Furthermore, recent findings indicate that vasoactive mediators released systemically by mast cells induce the production of S1P in non-hematopoietic compartments, where it plays a role in regulating the vascular tone and reducing the hypotension characteristic of the anaphylactic shock and thus helping the recovery. The dual actions of S1P, promoting the immediate response of mast cells, while controlling the systemic consequences of mast cell activity will be discussed in detail. PMID:21713655

  18. Segmentation of interstitial lung disease patterns in HRCT images

    NASA Astrophysics Data System (ADS)

    Dash, Jatindra K.; Madhavi, Vaddepalli; Mukhopadhyay, Sudipta; Khandelwal, Niranjan; Kumar, Prafulla

    2015-03-01

    Automated segmentation of pathological bearing region is the first step towards the development of lung CAD. Most of the work reported in the literature related to automated analysis of lung tissue aims towards classification of fixed sized block into one of the classes. This block level classification of lung tissues in the image never results in accurate or smooth boundaries between different regions. In this work, effort is taken to investigate the performance of three automated image segmentation algorithms those results in smooth boundaries among lung tissue patterns commonly encountered in HRCT images of the thorax. A public database that consists of HRCT images taken from patients affected with Interstitial Lung Diseases (ILDs) is used for the evaluation. The algorithms considered are Markov Random Field (MRF), Gaussian Mixture Model (GMM) and Mean Shift (MS). 2-fold cross validation approach is followed for the selection of the best parameter value for individual algorithm as well as to evaluate the performance of all the algorithms. Mean shift algorithm is observed as the best performer in terms of Jaccard Index, Modified Hausdorff Distance, accuracy, Dice Similarity Coefficient and execution speed.

  19. Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

    PubMed Central

    Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

    2012-01-01

    Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

  20. Antimicrobial Peptides and Innate Lung Defenses: Role in Infectious and Noninfectious Lung Diseases and Therapeutic Applications.

    PubMed

    Hiemstra, Pieter S; Amatngalim, Gimano D; van der Does, Anne M; Taube, Christian

    2016-02-01

    Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils in particular contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against microorganisms that are resistant against conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production, and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed.

  1. Supporting the validation of the new allergic and hypersensitivity conditions section of the World Health Organization International Classification of Diseases-11

    PubMed Central

    Calderon, Moises; Demoly, Pascal

    2016-01-01

    Background The new International Classification of Diseases (ICD)-11 "Allergic and hypersensitivity conditions" section has been constructed as a result of a detailed and careful action plan based on scientific evidences for the necessity of changes and collaboration with the World Health Organization (WHO) ICD-11 revision governance. All the efforts are being acknowledged by the Joint Allergy Academies. Objective Considering the new classification model addressed to the allergic and hypersensitivity conditions and following the ICD WHO agenda, we believe it is the appropriate time to start supporting the validation process in collaboration with the WHO ICD governance. Methods We conducted a mapping of ICD-10 allergic and hypersensitivity conditions in the ICD-11 beta phase structure and categorized the conditions as fitting by "precoordination," "postcoordination," "indexed to the ICD-11 Foundation," "no code fit properly" or "no correspondence" in the ICD-11. Results From overall 125 ICD-10 entities spread in 6 chapters, 57.6% were able to be precoordinated, 4% postcoordinated, 12% indexed to the Foundation, 9.6% had no code fitting properly and 18.6% had no correspondence in the ICD-11 framework. Conclusion We have been able to demonstrate that 83.2% of the ICD-10 allergic and hypersensitivity conditions could be captured by the current ICD-11 beta draft framework. We strongly believe that our findings constitute a key step forward for a softer transition of the ICD-10 allergic and hypersensitivity conditions to the ICD-11, supporting the WHO in this process as well as strengthening the visibility of the Allergy specialty and ensuring quality management of allergic patients. PMID:27489786

  2. SUSCEPTIBILITY FACTORS FOR THE DEVELOPMENT OF ALLERGIC LUNG DISEASE AND ASTHMA

    EPA Science Inventory


    Environmental Issue: More than 17 million people in the United States had asthma in 1998, which represents a doubling of the incidence in the previous 20 years. Since changes in the genetic makeup of the population take generations to occur, this increase must be related to ...

  3. Immunoglobulin G4-related lung disease: A disease with many different faces

    PubMed Central

    Hui, Philip; Mattman, André; Wilcox, Pearce G; Wright, Joanne L; Sin, Don D

    2013-01-01

    Immunoglobulin (Ig) G4-related lung disease is a fibroinflammatory entity that presents in protean ways. Diagnostically, IgG4-related lung disease requires a high clinical index of suspicion complemented by elevated serum IgG4 levels and/or biopsy that shows the characteristic pathological features. The disease is almost always responsive to systemic corticosteroids. However, relapse is common following their discontinuation. The authors present three cases to highlight the diverse clinical features, and to illustrate the diagnostic and therapeutic approaches to this disease. PMID:24093112

  4. IκB kinase β inhibitor, IMD-0354, prevents allergic asthma in a mouse model through inhibition of CD4(+) effector T cell responses in the lung-draining mediastinal lymph nodes.

    PubMed

    Maślanka, Tomasz; Otrocka-Domagała, Iwona; Zuśka-Prot, Monika; Mikiewicz, Mateusz; Przybysz, Jagoda; Jasiecka, Agnieszka; Jaroszewski, Jerzy J

    2016-03-15

    IκB kinase (IKK) is important for nuclear factor (NF)-κB activation under inflammatory conditions. It has been demonstrated that IMD-0354, i.e. a selective inhibitor of IKKβ, inhibited allergic inflammation in a mouse model of ovalbumin (OVA)-induced asthma. The present study attempts to shed light on the involvement of CD4(+) effector (Teff) and regulatory (Treg) T cells in the anti-asthmatic action of IMD-0354. The animals were divided into three groups: vehicle treated, PBS-sensitized/challenged mice (PBS group); vehicle treated, OVA-sensitized/challenged mice (OVA group); and IMD-0354-treated, OVA-sensitized/challenged mice. The analyzed parameters included the absolute counts of Treg cells (Foxp3(+)CD25(+)CD4(+)), activated Teff cells (Foxp3(-)CD25(+)CD4(+)) and resting T cells (CD25(-)CD4(+)) in the mediastinal lymph nodes (MLNs), lungs and peripheral blood. Moreover, lung histopathology was performed to evaluate lung inflammation. It was found that the absolute number of cells in all studied subsets was considerably increased in the MLNs and lungs of mice from OVA group as compared to PBS group. All of these effects were fully prevented by treatment with IMD-0354. Histopathological examination showed that treatment with IMD-0354 protected the lungs from OVA-induced allergic airway inflammation. Our results indicate that IMD-0354 exerts anti-asthmatic action, at least partially, by blocking the activation and clonal expansion of CD4(+) Teff cells in the MLNs, which, consequently, prevents infiltration of the lungs with activated CD4(+) Teff cells. The beneficial effects of IMD-0354 in a mouse model of asthma are not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of inducible Treg cells. PMID:26868187

  5. Neural network approach for differential diagnosis of interstitial lung diseases

    NASA Astrophysics Data System (ADS)

    Asada, Naoki; Doi, Kunio; MacMahon, Heber; Montner, Steven M.; Giger, Maryellen L.; Abe, Chihiro; Wu, Chris Y.

    1990-07-01

    A neural network approach was applied for the differential diagnosis of interstitial lung diseases. The neural network was designed for distinguishing between 9 types of interstitial lung diseases based on 20 items of clinical and radiographic information. A database for training and testing the neural network was created with 10 hypothetical cases for each of the 9 diseases. The performance of the neural network was evaluated by ROC analysis. The optimal parameters for the current neural network were determined by selecting those yielding the highest ROC curves. In this case the neural network consisted of one hidden layer including 6 units and was trained with 200 learning iterations. When the decision performances of the neural network chest radiologists and senior radiology residents were compared the neural network indicated high performance comparable to that of chest radiologists and superior to that of senior radiology residents. Our preliminary results suggested strongly that the neural network approach had potential utility in the computer-aided differential diagnosis of interstitial lung diseases. 1_

  6. Prevalence and prognosis of unclassifiable interstitial lung disease.

    PubMed

    Ryerson, Christopher J; Urbania, Thomas H; Richeldi, Luca; Mooney, Joshua J; Lee, Joyce S; Jones, Kirk D; Elicker, Brett M; Koth, Laura L; King, Talmadge E; Wolters, Paul J; Collard, Harold R

    2013-09-01

    The aim of this study was to determine the prevalence, characteristics and outcomes of patients with unclassifiable interstitial lung disease (ILD) and to develop a simple method of predicting disease behaviour. Unclassifiable ILD patients were identified from an ongoing longitudinal cohort. Unclassifiable ILD was diagnosed after a multidisciplinary review did not secure a specific ILD diagnosis. Clinical characteristics and outcomes were compared with idiopathic pulmonary fibrosis (IPF) and non-IPF ILDs. Independent predictors of mortality were determined using Cox proportional-hazards analysis to identify subgroups with distinct disease behaviour. Unclassifiable ILD was diagnosed in 10% of the ILD cohort (132 out of 1370 patients). The most common reason for being unclassifiable was missing histopathological assessment due to a high risk of surgical lung biopsy. Demographic and physiological features of unclassifiable ILD were intermediate between IPF and non-IPF disease controls. Unclassifiable ILD had longer survival rates when compared to IPF on adjusted analysis (hazard ratio 0.62, p = 0.04) and similar survival compared to non-IPF ILDs (hazard ratio 1.54, p = 0.12). Independent predictors of survival in unclassifiable ILD included diffusion capacity of the lung for carbon monoxide (p = 0.001) and a radiological fibrosis score (p = 0.02). Unclassifiable ILD represents approximately 10% of ILD cases and has a heterogeneous clinical course, which can be predicted using clinical and radiological variables.

  7. Pathogenesis and therapeutics of interstitial lung disease in systemic sclerosis.

    PubMed

    Castillo-Tandazo, Wilson; González, José; Flores-Fortty, Adolfo

    2013-01-01

    Interstitial lung disease is a common manifestation in systemic sclerosis and is considered as one of the two main causes of death among these patients. Although the pathogenesis of interstitial lung disease related to systemic sclerosis (SSc-ILD) is very complex and not yet fully understood, diverse mechanisms such as vascular injury, altered immunological response and inflammatory activation have been proposed. Vascular injury is considered as the earliest event in the pathogenesis of this disease and has been associated with an excessive formation of alveolar capillaries, circulating endothelial cells, and increased expression of endothelin-1. Different cells like myofibroblasts, fibroblasts, endothelial cells and T lymphocytes are involved in the inflammatory activation. Meanwhile, lymphocyte activation, release of several cytokines and autoantibody production play an important role in the immunological response. To date, the treatment of SSc-ILD is not totally defined, as studies have shown mixed results. Given the high progression of the disease, it is difficult to enroll patients for clinical trials. Therefore, there is lack of evidence to guide therapeutic approaches. Throughout this paper, we present evidence supporting that the combination of glucocorticoids and cyclophosphamide is considered the best regimen for patients with SSc-ILD. In addition, we present data regarding the use of azathioprine, mycophenolate, anti-fibrosing agents, bosentan, rituximab, and imatinib mesylate as alternative therapies. Finally, for patients who are unresponsive to pharmacologic interventions, we present data regarding the efficacy of highdose immunosuppression with autologous transplantation of hematopoietic stem cells, and lung transplantation.

  8. Microstructural alterations of sputum in cystic fibrosis lung disease

    PubMed Central

    Duncan, Gregg A.; Jung, James; Joseph, Andrea; Thaxton, Abigail L.; West, Natalie E.; Boyle, Michael P.; Hanes, Justin

    2016-01-01

    The stasis of mucus secretions in the lungs of cystic fibrosis (CF) patients leads to recurrent infections and pulmonary exacerbations, resulting in decreased survival. Prior studies have assessed the biochemical and biophysical features of airway mucus in individuals with CF. However, these measurements are unable to probe mucus structure on microscopic length scales relevant to key players in the progression of CF-related lung disease, namely, viruses, bacteria, and neutrophils. In this study, we quantitatively determined sputum microstructure based on the diffusion of muco-inert nanoparticle probes in CF sputum and found that a reduction in sputum mesh pore size is characteristic of CF patients with reduced lung function, as indicated by measured FEV1. We also discovered that the effect of ex vivo treatment of CF sputum with rhDNase I (Pulmozyme) on microstructure is dependent upon the time interval between the most recent inhaled rhDNase I treatment and the sample collection. Microstructure of mucus may serve as a marker for the extent of CF lung disease and as a parameter for assessing the effectiveness of mucus-altering agents. PMID:27812540

  9. The Microbiome and Mental Health: Looking Back, Moving Forward with Lessons from Allergic Diseases

    PubMed Central

    Logan, Alan C.; Jacka, Felice N.; Craig, Jeffrey M.; Prescott, Susan L.

    2016-01-01

    Relationships between gastrointestinal viscera and human emotions have been documented by virtually all medical traditions known to date. The focus on this relationship has waxed and waned through the centuries, with noted surges in interest driven by cultural forces. Here we explore some of this history and the emerging trends in experimental and clinical research. In particular, we pay specific attention to how the hygiene hypothesis and emerging research on traditional dietary patterns has helped re-ignite interest in the use of microbes to support mental health. At present, the application of microbes and their structural parts as a means to positively influence mental health is an area filled with promise. However, there are many limitations within this new paradigm shift in neuropsychiatry. Impediments that could block translation of encouraging experimental studies include environmental forces that work toward dysbiosis, perhaps none more important than westernized dietary patterns. On the other hand, it is likely that specific dietary choices may amplify the value of future microbial-based therapeutics. Pre-clinical and clinical research involving microbiota and allergic disorders has predated recent work in psychiatry, an early start that provides valuable lessons. The microbiome is intimately connected to diet, nutrition, and other lifestyle variables; microbial-based psychopharmacology will need to consider this contextual application, otherwise the ceiling of clinical expectations will likely need to be lowered. PMID:27121424

  10. The Microbiome and Mental Health: Looking Back, Moving Forward with Lessons from Allergic Diseases.

    PubMed

    Logan, Alan C; Jacka, Felice N; Craig, Jeffrey M; Prescott, Susan L

    2016-05-31

    Relationships between gastrointestinal viscera and human emotions have been documented by virtually all medical traditions known to date. The focus on this relationship has waxed and waned through the centuries, with noted surges in interest driven by cultural forces. Here we explore some of this history and the emerging trends in experimental and clinical research. In particular, we pay specific attention to how the hygiene hypothesis and emerging research on traditional dietary patterns has helped re-ignite interest in the use of microbes to support mental health. At present, the application of microbes and their structural parts as a means to positively influence mental health is an area filled with promise. However, there are many limitations within this new paradigm shift in neuropsychiatry. Impediments that could block translation of encouraging experimental studies include environmental forces that work toward dysbiosis, perhaps none more important than westernized dietary patterns. On the other hand, it is likely that specific dietary choices may amplify the value of future microbial-based therapeutics. Pre-clinical and clinical research involving microbiota and allergic disorders has predated recent work in psychiatry, an early start that provides valuable lessons. The microbiome is intimately connected to diet, nutrition, and other lifestyle variables; microbial-based psychopharmacology will need to consider this contextual application, otherwise the ceiling of clinical expectations will likely need to be lowered. PMID:27121424

  11. [Basophil count of the newborn is not useful in prediction of allergic diseases].

    Pub