Journal of Asthma and Allergy

Incidence and risk factors for exacerbations of asthma during pregnancy

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Authors: Ali Z, Ulrik CS

Published Date May 2013 Volume 2013:6 Pages 53 - 60

DOI: http://dx.doi.org/10.2147/JAA.S43183

Received:	24 January 2013
Accepted:	20 March 2013
Published:	06 May 2013

Zarqa Ali, Charlotte Suppli Ulrik

Department of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, Denmark

Background: Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma during pregnancy.
Methods: A narrative literature review was carried out using the PubMed database.
Results: During pregnancy, up to 6% of women with asthma are hospitalized for an acute exacerbation. The maternal immune system is characterized by a very high T-helper-2:T-helper-1 cytokine ratio during pregnancy and thereby provides an environment essential for fetal survival but one that may aggravate asthma. Cells of the innate immune system such as monocytes and neutrophils are also increased during pregnancy, and this too can exacerbate maternal asthma. Severe or difficult-to-control asthma appears to be the major risk factor for exacerbations during pregnancy, but studies also suggest that nonadherence with controller medication and viral infections are important triggers of exacerbations during pregnancy. So far, inconsistent findings have been reported regarding the effect of fetal sex on exacerbations during pregnancy. Other risk factors for exacerbation during pregnancy include obesity, ethnicity, and reflux, whereas atopy does not appear to be a risk factor.
Discussion: The incidence of asthma exacerbations during pregnancy is disturbingly high. Severe asthma – better described as difficult-to-control asthma – nonadherence with controller therapy, viral infections, obesity, and ethnicity are likely to be important risk factors for exacerbations of asthma during pregnancy, whereas inconsistent findings have been reported with regard to the importance of sex of the fetus.

Keywords: acute exacerbations, pregnancy, asthma severity, incidence, risk factors



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 Biologics: Targets and Therapy

Hereditary angioedema: epidemiology, management, and role of icatibant

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Authors: Ghazi A, Grant JA

Published Date May 2013 Volume 2013:7 Pages 103 - 113

DOI: http://dx.doi.org/10.2147/BTT.S27566

Received:	21 January 2013
Accepted:	02 April 2013
Published:	03 May 2013

Aasia Ghazi, J Andrew Grant

University of Texas Medical Branch, Division of Allergy and Clinical Immunology, Galveston, TX, USA

Abstract: Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert^®, Cinryze^®, and Cetor^®) and recombinant (Rhucin^® and Ruconest™) C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor^®), and bradykinin B2 receptor antagonist-icatibant (Firazyr^®). Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr^®), a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial economic burdens. The timely and proper use of disease-specific treatments could improve patients' quality of life, reduce the disease-specific morbidity and mortality, and, last but not least, reduce costs associated with hospitalizations and emergency room visits. Therefore, the paradigm of HAE treatment has the potential to evolve significantly, thereby exponentially improving a patient’s quality of life.

Keywords: hereditary angioedema, icatibant, C1 inhibitor, bradykinin



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Systemic inflammation, depression and obstructive pulmonary function

Research

Systemic inflammation, depression and obstructive pulmonary function: a population-based study

Yanxia Lu, Lei Feng, Liang Feng, Ma Shwe Nyunt, Keng Bee Yap and Tze Pin Ng

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Respiratory Research 2013, 14:53 doi:10.1186/1465-9921-14-53

Published: 15 May 2013

Abstract (provisional)

Background

Levels of Interleukin-6 (IL-6) and C-creative protein (CRP) indicating systemic inflammation are known to be elevated in chronic diseases including chronic obstructive pulmonary disease (COPD) and depression. Comorbid depression is common in patients with COPD, but no studies have investigated whether proinflammatory cytokines mediate the association between pulmonary function and depressive symptoms in healthy individuals with no known history of obstructive pulmonary diseases.

Methods

In a population-based sample (n = 2077) of individuals aged 55 and above with no known history of obstructive pulmonary disease in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the relationships between IL-6 and CRP, depressive symptoms (GDS-15 >=5) and obstructive pulmonary function (FEV1% predicted and FEV1/FVC% predicted).

Results

High serum levels of IL-6 and CRP were associated with greater prevalence of depressive symptoms (p < 0.05). High IL-6, high CRP and depressive symptoms were independently associated with decreased FEV1% predicted and FEV1/FVC% predicted predicted after adjusting for smoking status, BMI and number of chronic inflammatory diseases. Increasing grades of combination of inflammatory markers and/or depressive symptoms was associated with progressive increases in pulmonary obstruction. In hierarchical models, the significant association of depressive symptoms with pulmonary obstruction was reduced by the presence of IL-6 and CRP.

Conclusions

This study found for the first time an association of depressive symptoms and pulmonary function in older adults which appeared to be partly mediated by proinflammatory cytokines. Further studies should be conducted to investigate proinflammatory immune markers and depressive symptoms as potential phenotypic indicators for chronic obstructive airway disorders in older adults.

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Original Article

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P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps

1. Rachel E. Feldman BA¹, 
2. Allen C. Lam MD¹, 
3. Peter M. Sadow MD, PhD², 
4. Benjamin S. Bleier MD^1,*

Article first published online: 15 MAY 2013

DOI: 10.1002/alr.21176

© 2013 The Authors. International Forum of Allergy & Rhinology, published by Wiley Periodicals, Inc., on behalf of ARS-AAOA, LLC.

Issue

International Forum of Allergy & Rhinology

Early View (Online Version of Record published before inclusion in an issue)

Additional Information(Show All)

How to CiteAuthor InformationPublication History

1. Potential conflict of interest: B.S.B. is an inventor on a provisional patent regarding modulation of P-glycoprotein in the treatment of chronic rhinosinusitis.

• Abstract
• Article
• References
• Cited By

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Keywords:

• chronic sinusitis;
• nasal polyposis;
• P-glycoprotein;
• active efflux pumps;
• inflammation;
• Th1;
• Th2;
• eosinophilia;
• eosinophilic chronic rhinosinusitis;
• Lund-Mackay score

Background

P-glycoprotein (P-gp) is a membrane-bound efflux pump that is upregulated in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and participates in epithelial cytokine secretion. Eosinophilic CRS (ECRS) shares a similar cytokine profile with CRSwNP and is associated with significant inflammation and poor surgical outcomes. The goal of this study is to determine if P-gp expression is associated with degree of eosinophilia and severity of radiographic inflammation in patients with CRS without polyps (CRSsNP).

Methods

An institutional review board (IRB)-approved study using sinus tissue in 39 steroid-naive patients with CRS. P-gp expression was calculated using quantitative fluorescent immunohistochemistry (Q-FIHC) to generate an epithelial to background staining ratio. Patients were stratified into low and high epithelial expression groups (<3 2-tailed="" a="" and="" average="" calculated="" compared="" em="" eosinophils="" field="" high="" hpf="" lund-mackay="" nbsp="" p-gp="" per="" powered="" ratios="" respectively="" scores="" staining="" student="" style="background-color: transparent; border: 0px; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" using="" were="" with="">t

 test.

Results

Among the 39 patients, 7 (17.95%) had high P-gp expression ratios (mean ± SD, 4.86 ± 1.33) while 32 (82.05%) had low expression ratios (1.91 ± 0.45). The number of eosinophils/hpf were significantly greater in the high P-gp expression group as compared to the low expression group (62.38 ± 83.69 vs 5.11 ± 10.12, p = 0.0003). The Lund-Mackay scores were significantly greater in the high P-gp expression group as compared to the low expression group (11.86 ± 2.79 vs 6.84 ± 4.19, p = 0.005).

Conclusion

P-gp is known to be overexpressed in CRSwNP. This study suggests that among patients with CRSsNP, P-gp is similarly overexpressed in those with high tissue eosinophilia and correlates with severity of radiographic inflammation.

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Cutaneous lupus erythematosus: clinical aspects and molecular pathogenesis

1. V. Oke^*, 
2. M. Wahren-Herlenius

Article first published online: 14 MAR 2013

DOI: 10.1111/joim.12057

© 2013 The Association for the Publication of the Journal of Internal Medicine

Issue

Journal of Internal Medicine

Volume 273, Issue 6, pages 544–554, June 2013

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How to CiteAuthor InformationPublication History

• Abstract
• Article
• References
• Cited By

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Keywords:

• autoimmunity;
• cutaneous lupus erythematosus;
• Ro52;
• systemic lupus erythematosus;
• ultraviolet radiation

Abstract

Lupus erythematosus (LE) is an autoimmune disease with diverse clinical manifestations ranging from limited cutaneous (CLE) to potentially life-threatening systemic disease (SLE). Susceptibility to LE arises from genetic variation in multiple loci, and disease activity is provoked by exogenous or endogenous trigger(s), the best characterized of which is exposure to ultraviolet radiation (UVR). Amongst patients with LE, a cluster of photosensitive subjects with cutaneous lesions and positivity for anti-Ro/SSA autoantibodies have been described. The Ro52 antigen belongs to the tripartite motif protein family and has E3 ligase activity. New data reveal that Ro52 ubiquitinates interferon regulatory factors and modulates their transcriptional activity, indicating an important role for Ro52 in inflammation as a negative feedback regulator. Our findings indicate that UVR exposure induces upregulation of Ro52 in the CLE target cell, the keratinocyte, and that Ro52 is upregulated in spontaneous and UVR-induced CLE lesions. Recently described functional analysis of Ro52-deficient mice revealed that loss of Ro52 results in uncontrolled inflammation in response to minor skin injury leading to an LE-like condition. In summary, emerging data suggest that abnormal function or regulation of Ro52 contributes to the pathogenesis of UVR-induced CLE in genetically susceptible individuals. Ro52 may thus be an interesting therapeutic target, as its activation could contribute to downregulation of the chronic inflammatory process in LE. Here, we review the available data on the pathogenesis of CLE and, in particular, the role of the Ro52 autoantigen.

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Dr. David Peden discusses the effect of air pollution on asthma and respiratory health.

Dr. David Peden discusses the effect of air pollution on asthma and respiratory health. Held on April 19, 2013.


About Conferences On-Line Allergy

COLA (Conferences On-Line Allergy) is a live series of online allergy conferences held at Children's Mercy Hospital in Kansas City, Missouri. World experts give presentations on topics related to allergy and immunology. Live conferences are held on Monday and Friday from 10-noon (central time). They can be joined by going to http://www.childrensmercy.org/cola

Charles Barnes describes laboratory methods to measure immune complexes and their clinical uses.

Dr 

Charles Barnes describes laboratory methods to measure immune complexes and their clinical uses. Held on March 8, 2013.


About Conferences On-Line Allergy

COLA (Conferences On-Line Allergy) is a live series of online allergy conferences held at Children's Mercy Hospital in Kansas City, Missouri. World experts give presentations on topics related to allergy and immunology. Live conferences are held on Monday and Friday from 10-noon (central time). They can be joined by going to http://www.childrensmercy.org/cola

Dr. Jonathan Bernstein describes various aspects of reproductive immunology.

Dr. Jonathan Bernstein describes various aspects of reproductive immunology. Held on March 29, 2013.

About Conferences On-Line Allergy

COLA (Conferences On-Line Allergy) is a live series of online allergy conferences held at Children's Mercy Hospital in Kansas City, Missouri. World experts give presentations on topics related to allergy and immunology. Live conferences are held on Monday and Friday from 10-noon (central time). They can be joined by going to http://www.childrensmercy.org/cola