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THE JOURNAL OF
AllergyANDClinicalImmunology
� 2013 American A
The Journal of Allergy and Cpaid at New York, NY, and aSubscription Customer Servi
10A March 2013
VOLUME 131 d NUMBER 3
OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF ALLERGY, ASTHMA & IMMUNOLOGY
News beyond our pages 625
Marc E. Rothenberg, MD, PhD, Jean Bousquet, MD, and Patricia C. Fulkerson, MD, PhDReviews and feature articles
Clinical reviews in allergy and immunology
Clinical phenotypes of chronic obstructive pulmonary disease and asthma: Recent advances
627Brendan J. Carolan, MD, and E. Rand Sutherland, MD, MPH, Denver, ColoThis article has been selected for the JACI Journal Club blog. Visit www.jaci-online.blogspot.com to join the discussion.
Continuing Medical Education examination: Clinical phenotypes of chronic obstructivepulmonary disease and asthma: Recent advances
635
Continued on page 12A
This month’s theme: Asthma-COPD link
About the cover
Asthma and COPD are common respiratory diseases. Asthma frequently starts inchildhood, and COPD starts in adulthood. Clinicians question the similarities anddifferences between these two diseases. This is especially important as we evaluate thediagnosis in adults and seek to manage each disease. Although some of the medicationsused for COPD and asthma are similar, there are some unique differences due to thepathology and clinical response to therapy. This month’s theme is centered on differencesin asthma and COPD. In a Clinical Reviews article, Brendan J. Carolan and E. RandSutherland (p 627) discuss recent advances in understanding clinical phenotypes of COPDin relation to asthma. They conclude that it is likely that further elucidating theheterogeneity of COPD and asthma through clinical and biologic phenotyping will allowgreater understanding of pathogenetic mechanisms and for more directed management,especially when patients are not controlled with first-line modalities. As part of ourMechanisms of Allergic Diseases series, Peter J. Barnes (p 636) discusses corticosteroidresistance in asthma and COPD.He indicates that identifying themolecular mechanisms ofsteroid resistance in asthma and COPD may lead to more effective anti-inflammatorytreatments in the future. This month’s cover image points out some of the differences inpathophysiology between asthma and COPD.
Cover concept by Peter Barnes, Donald Y. M. Leung, and Boyd Jacobson
cademy of Allergy, Asthma & Immunology
linical Immunology (ISSN: 0091-6749) is published monthly by Elsevier Inc., 360 Park Avenue South, New York, NY 10010-1710. Periodicals postagedditional mailing offices. POSTMASTER: Send address changes to The Journal of Allergy and Clinical Immunology, Elsevier Health Sciences Division,ce, 3251 Riverport Lane, Maryland Heights, MO 63043.
J ALLERGY CLIN IMMUNOL
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The Journ
the Journa
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article firs
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12A March
Mechanisms of allergic diseases
Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease
636 Peter J. Barnes, FRS, FMedSci, London, United KingdomCurrent perspectives
Small-airways dysfunction associates with respiratory symptoms and clinical features ofasthma: A systematic review
646
Erica van der Wiel, MD, Nick H. T. ten Hacken, MD, PhD, Dirkje S. Postma, MD, PhD, and Maarten van den Berge, MD, PhD,Groningen, The Netherlands
Allergy and clinical immunology around the world
Combined immunodeficiency: The Middle East experience
658 Waleed Al-Herz, MD, and Hamoud Al-Mousa, MD, Safat and Kuwait City, Kuwait, and Riyadh, Saudi ArabiaAdvances in allergy, asthma, and immunology series 2013
Advances in mechanisms of allergy and clinical immunology in 2012
661 Bruce S. Bochner, MD, Marc E. Rothenberg, MD, PhD, Joshua A. Boyce, MD, and Fred Finkelman, PhD, Baltimore, Md, Cincinnati,Ohio, and Boston, MassAdvances in environmental and occupational disorders in 2012
668 David B. Peden, MD, and Robert K. Bush, MD, Chapel Hill, NC, and Madison, WisAdvances in basic and clinical immunology in 2012
675 Javier Chinen, MD, PhD, Luigi D. Notarangelo, MD, and William T. Shearer, MD, PhD, Houston, Tex, and Boston, MassContinued on page 14A
Editors’ Choice
Online Repository material
Video available online at www.jacionline.org
Theme article
CME activity available online at www.jacionline.org
al of Allergy and Clinical Immunology posts in-press articles online in advance of their appearance in the print edition of
l. They are available at the JACI Web site at www.jacionline.org at the ‘‘Articles in Press’’ link, as well as at Elsevier’s
irect Web site, www.sciencedirect.com. Each print article will acknowledge the e-publication date (the date when the
t appeared online). As soon as an article is published online, it is fully citable through use of its Digital Object Identifier
ease visit the JACI Web site and view our hot-off-the-wire articles through the ‘‘Articles in Press’’ link.
2013 J ALLERGY CLIN IMMUNOL
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14A March
The Editors’ choice 683
Donald Y. M. Leung, MD, PhD, Stanley J. Szefler, MD, and the Associate Editors of the JACIAsthma and lower airway disease
Examination of the relationship between variation at 17q21 and childhood wheezephenotypes
685
Raquel Granell, PhD, A. John Henderson, MD, Nicholas Timpson, PhD, Beate St. Pourcain, PhD, John P. Kemp, PhD,Susan M. Ring, PhD, Karen Ho, PhD, Stephen B. Montgomery, PhD, Emmanouil T. Dermitzakis, PhD, David M. Evans, PhD,and Jonathan A. C. Sterne, PhD, Bristol and Cambridge, United Kingdom, Geneva, Switzerland, and Stanford, Calif
Asthma-related genetic variants on chromosome 17 are associated with specific wheezing phenotypes in
young children. Understanding the causal mechanisms driving these associations could help predict disease in
children presenting with wheezing illness in the preschool years.
The Asthma Control Test and Asthma Control Questionnaire for assessing asthma control:Systematic review and meta-analysis
695
Chun E. Jia, MD, Hong Ping Zhang, MD, Yan Lv, MD, Rui Liang, MD, Yun Qiu Jiang, MD, Heather Powell, MMedSci,Juan Juan Fu, MD, Lei Wang, MD, Peter Gerard Gibson, MBBS, and Gang Wang, MD, PhD, Chengdu, China, and New Lambton,Australia
The Asthma Control Test provided good accuracy for assessing controlled and not-well-controlled asthma,
and Asthma Control Questionnaire 7 (ACQ-7) and ACQ-6 accurately assessed not-well-controlled asthma at
prespecified cutoff points, but they had significant differences after adjustment for potential factors.
Work-exacerbated asthma and occupational asthma: Do they really differ?
704Catherine Lemiere, MD, MSc, Louis-Phillippe Boulet, MD, Simone Chaboillez, RT, Amelie Forget, MSc, Samah Chiry, MD, MSc,Helene Villeneuve, RN, Philippe Prince, MSc, Karim Maghni, DSc, PhD, Wendy A. Kennedy, PhD, and Lucie Blais, PhD, Montreal and Quebec City, Quebec, CanadaThe difference between the inflammatory phenotypes observed in work-exacerbated asthma and occupational
asthma (OA) can help in the diagnosis of these conditions. A proper diagnosis and management of OA is
associated with a significant reduction in health care–related costs.
A population analysis of prescriptions for asthma medications during pregnancy
711 Priscilla A. Zetstra–van der Woude, MSc, J. Sebastiaan Vroegop, MD, H. Jens Bos, and Lolkje T. W. de Jong–van den Berg, Prof Dr,Groningen, The NetherlandsMany women stop receiving prescriptions for asthma medications when they get pregnant—especially
prescriptions for long-acting bronchodilators. This can lead to poor asthma control and increased risk of
exacerbation.
Peripheral airway impairment measured by oscillometry predicts loss of asthma control inchildren
718
Yixin Shi, MS, Anna S. Aledia, BS, Stanley P. Galant, MD, and Steven C. George, MD, PhD, Irvine and Orange, Calif
In a longitudinal study design, children with controlled mild-to-moderate asthma at baseline but increased
peripheral airway indices of impulse oscillometry were more likely to lose asthma control over an 8- to
12-week period.
Continued on page 17A
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J ALLERGY
The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: A systematicreview and meta-analysis of randomized controlled trials
724
Matthew A. Rank, MD, John B. Hagan, MD, Miguel A. Park, MD, Jenna C. Podjasek, MD, Shefali A. Samant, MD,
Gerald W. Volcheck, MD, Patricia J. Erwin, MLS, and Colin P. West, MD, PhD, Rochester, MinnThe relative risk of an asthma exacerbation in patients who stop low-dose inhaled corticosteroids is 2.35
(95% CI, 1.88-2.92; P < .001) compared with those who continued inhaled corticosteroids in randomized
controlled trials.
Maternal smoking affects lung function and airway inflammation in young children withmultiple-trigger wheeze
730
Satu Kalliola, MD, Anna S. Pelkonen, MD, PhD, L. Pekka Malmberg, MD, PhD, Seppo Sarna, PhD, Mauri Hamalainen, PhD,Ilkka Mononen, MD, PhD, and Mika J. Makela, MD, PhD, Helsinki and Turku, Finland
Effect of parental smoking was studied in steroid-naive preschool-aged children with multiple-trigger wheeze.
Maternal smoking was associated with increased FENO values and poorer lung function; the effect was
dose-dependent.
Prenatal and postnatal bisphenol A exposure and asthma development among inner-citychildren
736
Kathleen M. Donohue, MD, Rachel L. Miller, MD, Matthew S. Perzanowski, PhD, Allan C. Just, PhD, Lori A. Hoepner, MS,Srikesh Arunajadai, PhD, Stephen Canfield, MD, PhD, David Resnick, MD, Antonia M. Calafat, PhD, Frederica P. Perera, DrPH,and Robin M. Whyatt, DrPH, New York, NY, and Atlanta, Ga
This is the first cohort study to report an association between postnatal environmental exposure to bisphenol
A and asthma in young children.
Gender differences in the bronchoalveolar lavage cell proteome of patients with chronicobstructive pulmonary disease
743
Maxie Kohler, PhD, AnnSofi Sandberg, MSc, Sanela Kjellqvist, PhD, Andreas Thomas, PhD, Reza Karimi, MD, Sven Nyren, MD, PhD,Anders Eklund, MD, PhD, Mario Thevis, PhD, C. Magnus Skold, MD, PhD, and Asa M. Wheelock, PhD, Stockholm, Sweden, andCologne, Germany
This study links changes in the proteome to phenotypic sex differences in chronic obstructive pulmonary
disease. It provides new potential protein biomarkers and proves that diagnosis, treatment, and the search for
new markers should be performed on a sex-specific basis.
A new short-term mouse model of chronic obstructive pulmonary disease identifies a role formast cell tryptase in pathogenesis
752
Emma L. Beckett, B Biomed Sci, Richard L. Stevens, PhD, Andrew G. Jarnicki, PhD, Richard Y. Kim, B Biomed Sci, Irwan Hanish, BSc,
Nicole G. Hansbro, PhD, Andrew Deane, BSc, Simon Keely, PhD, Jay C. Horvat, PhD, Ming Yang, MD, PhD, Brian G. Oliver, PhD,Nico van Rooijen, PhD, Mark D. Inman, MD, PhD, Roberto Adachi, MD, Roy J. Soberman, MD, Sahar Hamadi,Peter A. Wark, MD, PhD, Paul S. Foster, PhD, and Philip M. Hansbro, PhD, Newcastle and Sydney, Australia, Boston, Mass,Amsterdam, The Netherlands, Hamilton, Ontario, Canada, and Houston, TexThe authors describe a mouse model of chronic obstructive pulmonary disease (COPD) that develops the
hallmark features of the disease in just 8 weeks. Using this experimental model, they discovered detrimental
roles for mast cell tryptase in the setting of COPD.
Continued on page 18A
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18A March
Effect of montelukast for treatment of asthma in cigarette smokers
763David Price, MD, Todor A. Popov, MD, Leif Bjermer, MD, Susan Lu, PharmD, Romana Petrovic, MS, Kristel Vandormael, MS,Anish Mehta, BA, Jolanta D. Strus, MD, Peter G. Polos, MD, and George Philip, MD, Aberdeen, United Kingdom, Sofia, Bulgaria, Lund, Sweden, and Whitehouse Station, NJIn asthmatic smokers, a common but seldom-studied patient population, montelukast (a leukotriene receptor
antagonist) and fluticasone (an inhaled corticosteroid) each significantly increased days with asthma control
during 6 months of treatment compared with placebo.
Rhinitis, sinusitis, and upper airway disease
Chronic rhinosinusitis with polyps and without polyps is associated with increased expressionof suppressors of cytokine signaling 1 and 3
772
Se Jin Park, MD, Tae Hoon Kim, MD, Young Joon Jun, MD, Seung Hoon Lee, MD, Hyei Yul Ryu, MD, Kwang Jin Jung, MD,Jong Yoon Jung, MD, Gyu Ho Hwang, MD, and Sang Hag Lee, MD, Seoul, South Korea
SOCS1 and SOCS3 were increased in chronic rhinosinusitis and can be upregulated by cytokines expressed
in chronic rhinosinusitis.
Atopic sensitization in the first year of life
781Martin Depner, PhD, Markus J. Ege, MD, Jon Genuneit, MD, Juha Pekkanen, MD, PhD, Marjut Roponen, PhD,Maija-Riitta Hirvonen, PhD, Jean-Charles Dalphin, MD, PhD, Vincent Kaulek, PhD, Susanne Krauss-Etschmann, MD, Josef Riedler, MD, Charlotte Braun-Fahrlander, MD, Caroline Roduit, MD, MPH, Roger Lauener, MD, Petra I. Pfefferle, PhD, DPH,Juliane Weber, MD, Erika von Mutius, MD, and the PASTURE Study Group, Munich, Ulm, and Marburg, Germany, Kuopio, Finland,Besancon, France, Schwarzach, Austria, and Basel, Davos, and Zurich, SwitzerlandWithin the first year of life, persistent sensitization to the same allergens was rare, whereas transient (at birth
only) and incident (at 12 months only) sensitization was seen in substantial proportions of children.
Atopic dermatitis and skin disease
IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze atage 3 years
789
Diana Raedler, PhD, Sabina Illi, PhD, Leonardo Araujo Pinto, MD, Erika von Mutius, MD, Thomas Illig, PhD, Michael Kabesch, MD,and Bianca Schaub, MD, Munich, Neuherberg, and Hannover, Germany, and Porto Alegre, Brazil
Carriers of IL10 single nucleotide polymorphisms showed modulated regulatory T-cell marker genes and
TH1/TH2 and proinflammatory cytokines associated with an increased risk of atopic dermatitis or wheeze
during the first 3 years of life.
Food, drug, insect sting allergy, and anaphylaxis
Empiric 6-food elimination diet induced and maintained prolonged remission in patientswith adult eosinophilic esophagitis: A prospective study on the food cause of the disease
797
Alfredo J. Lucendo, MD, PhD, FEBG, Angel Arias, BSc, MSc, Jesus Gonzalez-Cervera, MD, Jose Luis Yague-Compadre, MD,Danila Guagnozzi, MD, Teresa Angueira, MD, Susana Jimenez-Contreras, MD, Sonia Gonzalez-Castillo, MD,Benito Rodrıguez-Domıngez, MD, Livia C. De Rezende, MD, PhD, and Jose M. Tenias, MD, PhD, Ciudad Real, Spain
An empiric 6-food elimination diet induced remission in patients with active adult eosinophilic esophagitits
(EoE). Sequential food reintroduction identified trigger foods, the persistent avoidance of which led to
prolonged drug-free EoE remission. Allergy tests were neither sensitive nor specific in predicting EoE triggers.
This article has been selected for the JACI Journal Club blog. Visit www.jaci-online.blogspot.com to join the discussion.
Continued on page 20A
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The natural history of milk allergy in an observational cohort
805 Robert A. Wood, MD, Scott H. Sicherer, MD, Brian P. Vickery, MD, Stacie M. Jones, MD, Andrew H. Liu, MD,David M. Fleischer, MD, Alice K. Henning, MS, Lloyd Mayer, MD, A. Wesley Burks, MD, Alexander Grishin, PhD,Donald Stablein, PhD, and Hugh A. Sampson, MD, Baltimore and Rockville, Md, New York, NY, Chapel Hill, NC, Little Rock, Ark, andDenver, ColoIn this longitudinal study of infants presenting with milk allergy, approximately one half had resolved over
66 months of follow-up. Baseline milk IgE level, skin test wheal size, and atopic dermatitis severity were all
important predictors of resolution.
Editorial: Natural history of cow’s milk allergy
813 Jonathan M. Spergel, MD, PhD, Philadelphia, PaImmune deficiencies, infection, and systemic immune disorders
Reduced type I interferon production by dendritic cells and weakened antiviral immunity inpatients with Wiskott-Aldrich syndrome protein deficiency
815
Philipp A. Lang, MD, PhD, Namir Shaabani, MSc, Stephanie Borkens, MSc, Nadine Honke, MSc, Stefanie Scheu, PhD,Sarah Booth, MSc, Dirk Brenner, PhD, Andreas Meryk, MSc, Carmen Barthuber, MD, PhD, Mike Recher, MD, Tak W. Mak, PhD,Pamela S. Ohashi, PhD, Dieter Haussinger, MD, Gillian M. Griffiths, PhD, Adrian J. Thrasher, MD, PhD, Gerben Bouma, PhD,and Karl S. Lang, MD, PhD, Toronto, Ontario, Canada, Dusseldorf and Essen, Germany, Oxford and London, United Kingdom, andBasel, Switzerland
CD8+ T cell–mediated antiviral immunity is impaired in patients with Wiskott-Aldrich syndrome protein
deficiency, resulting in reduced viral clearance and enhanced immunopathology. Defective type I interferon
production by dendritic cells plays a linked and important contributory role.
Clinical outcome in IL-10– and IL-10 receptor–deficient patients with or withouthematopoietic stem cell transplantation
825
Karin R. Engelhardt, PhD, Neil Shah, MD, Intan Faizura-Yeop, MD, Dilara F. Kocacik Uygun, MD, Natalie Frede,Aleixo M. Muise, MD, PhD, Eyal Shteyer, MD, Serkan Filiz, MD, Ronnie Chee, MD, Mamoun Elawad, MD, Britta Hartmann, PhD,Peter D. Arkwright, MD, PhD, Christopher Dvorak, MD, Christoph Klein, MD, PhD, Jennifer M. Puck, MD, Bodo Grimbacher, MD,and Erik-Oliver Glocker, MD, London and Manchester, United Kingdom, Freiburg and Munich, Germany, Antalya, Turkey, Toronto,Ontario, Canada, Jerusalem, Israel, and San Francisco, Calif
This study describes patients with IL-10/IL-10 receptor deficiency and discusses tests needed to diagnose the
disease and how to manage the affected patients.
Thymic function in MHC class II–deficient patients
831 Atar Lev, MSc, Amos J. Simon, BSc, Arnon Broides, MD, Jacob Levi, MD, Ben Zion Garty, MD, Ester Rosenthal, MSc,Ninette Amariglio, PhD, Gideon Rechavi, MD, PhD, and Raz Somech, MD, PhD, Tel Hashomer, Beer Sheva, Petah Tiqwa, andTel Aviv, IsraelMHC class II–deficient patients have reduced thymic function, although they represent a severe T-cell
immunodeficiency that might be missed (false negative) by T-cell receptor excision circle analysis in DNA
from peripheral blood or Guthrie cards with dried blood spots.
Continued on page 21A
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J ALLERGY
Defective actin accumulation impairs human natural killer cell function in patients withdedicator of cytokinesis 8 deficiency
840
Melissa C. Mizesko, MD, Pinaki P. Banerjee, PhD, Linda Monaco-Shawver, BA, Emily M. Mace, PhD, William E. Bernal, MD,Julie Sawalle-Belohradsky, Bernd H. Belohradsky, MD, Valerie Heinz, Alexandra F. Freeman, MD, Kathleen E. Sullivan, MD, PhD,Steven M. Holland, MD, Troy R. Torgerson, MD, PhD, Waleed Al-Herz, MD, Janet Chou, MD, Imelda C. Hanson, MD,Michael H. Albert, MD, Raif S. Geha, MD, Ellen D. Renner, MD, and Jordan S. Orange, MD, PhD, Houston, Tex, Philadelphia, Pa,Munich, Germany, Bethesda, Md, Seattle, Wash, Kuwait City, Kuwait, and Boston, Mass
This article defines natural killer (NK) cell dysfunction in dedicator of cytokinesis 8 (DOCK8)–deficient
patients and an essential role for DOCK8 in NK cells. The authors propose that this immunologic
mechanism is central to DOCK8-deficient patient susceptibilities to viral infections and cancers.
Mechanisms of allergy and clinical immunology
The innate antiviral response upregulates IL-13 receptor a2 in bronchial fibroblasts
849Gemma Campbell-Harding, PhD, Hannah Sawkins, BSc, Nicole Bedke, PhD, Stephen T. Holgate, DM, Donna E. Davies, PhD,and Allison-Lynn Andrews, PhD, Southampton, United KingdomThis study demonstrates the upregulation of IL-13 receptor a2 (IL-13Ra2), a receptor normally associated
with the regulation of the TH2 cytokine IL-13, by IFN-b. Expression of IL-13Ra2 during viral infection
might lead to downregulation of TH2 responses.
Decoding asthma: Translating genetic variation in IL33 and IL1RL1 into diseasepathophysiology
856
Neomi S. Grotenboer, MSc, Maria E. Ketelaar, MSc, Gerard H. Koppelman, MD, PhD, and Martijn C. Nawijn, PhD, Groningen,The Netherlands
IL33 and IL1RL1 are important asthma genes that each carry multiple independent genetic signals associated
with asthma. This review discusses possible functional consequences of these genetic signals in the context of
asthma development.
The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma
866 Kai-Michael Beeh, MD, Frank Kanniess, MD, Frank Wagner, MD, Cordula Schilder, MD, Ingomar Naudts, MD,Anya Hammann-Haenni, PhD, Joerg Willers, PhD, Hans Stocker, PhD, Philipp Mueller, MD, Martin F. Bachmann, PhD, andWolfgang A. Renner, PhD, Wiesbaden, Lubeck, Berlin, Eisenach, and Rodgau, Germany, and Schlieren, SwitzerlandQbG10 has shown a good safety profile and offers the potential of an immune-modulating therapy without
the administration of allergen in patients with allergic asthma, as shown in this randomized,
placebo-controlled proof-of-concept study.
Triggering of specific Toll-like receptors and proinflammatory cytokines breaksallergen-specific T-cell tolerance in human tonsils and peripheral blood
875
Umut Can Kucuksezer, PhD, Oscar Palomares, PhD, Beate Ruckert, Tuomas Jartti, MD, Tuomo Puhakka, MD, Andreas Nandy, PhD,Bilun Gemicio�glu, MD, PhD, Heinz B. Fahrner, MD, Andreas Jung, MD, Gunnur Deniz, PhD, Cezmi A. Akdis, MD,and Mubeccel Akdis, MD, PhD, Davos and Chur, Switzerland, Istanbul, Turkey, Madrid, Spain, Turku and Pori, Finland, andReinbek, Germany
Innate immune response triggering of Toll-like receptor (TLR) 4 or TLR8 and the proinflammatory cytokine
IL-1b or IL-6 breaks allergen-specific CD4+ T-cell tolerance in human tonsils and peripheral blood.
Continued on page 25A
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J ALLERGY
Early-life cockroach allergen and polycyclic aromatic hydrocarbon exposures predictcockroach sensitization among inner-city children
886
Matthew S. Perzanowski, PhD, Ginger L. Chew, ScD, Adnan Divjan, BA, Kyung Hwa Jung, PhD, Robert Ridder, BS,Deliang Tang, PhD, Diurka Diaz, MA, Inge F. Goldstein, DrPH, Patrick L. Kinney, ScD, Andrew G. Rundle, DrPH,David E. Camann, MS, Frederica P. Perera, DrPH, and Rachel L. Miller, MD, New York, NY, and San Antonio, Tex
Combined exposure to cockroach allergen in kitchen dust and polycyclic aromatic hydrocarbons in air
measured prenatally predicted cockroach sensitization at the age of 5 to 7 years. The association was most
pronounced among children with the GSTM1 null mutation.
Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients
894 Bettina Levanen, PhD, Nirav R. Bhakta, MD, PhD, Patricia Torregrosa Paredes, MSc, Rebecca Barbeau, MSc, Stefanie Hiltbrunner, MS,Joshua L. Pollack, MSc, C. Magnus Skold, MD, PhD, Magnus Svartengren, PhD, Johan Grunewald, MD, PhD,Susanne Gabrielsson, PhD, Anders Eklund, MD, PhD, Britt-Marie Larsson, PhD, Prescott G. Woodruff, MD, PhD,David J. Erle, MD, PhD, and Asa M. Wheelock, PhD, Stockholm, Sweden, and San Francisco, CalifExpression profiling of exosomal microRNA (miRNA) from bronchoalveolar lavage fluid revealed significant
differences between healthy subjects and patients with asthma at unprovoked baseline levels. These miRNA
alterations were correlated with lung function, with indications of targeting the IL-13 pathway.
Editorial: The exosome in lung diseases: Message in a bottle
904 N. Tony Eissa, MD, Houston, TexLetters to the Editor
Mannitol test results in asthmatic adults receiving inhaled corticosteroids
906 John D. Brannan, PhD, Clare P. Perry, BSc, and Sandra D. Anderson, PhD, DSc, Westmead and Camperdown, AustraliaSimilar to reported data for the methacholine bronchial provocation test, the diagnostic sensitivity of inhaled
mannitol is reduced in a Caucasian adult population taking regular inhaled corticosteroids.
Possible role of TH17 cells in the pathogenesis of Stevens-Johnson syndrome and toxicepidermal necrolysis
907
Yuichi Teraki, MD, Misaki Kawabe, MD, and Seiichi Izaki, MD, Saitama, Japan
TH17 cells might be involved in the development of Stevens-Johnson syndrome (SJS)/toxic epidermal
necrolysis (TEN) as enhancers and might determine the outcome of SJS/TEN.
Treatment of attacks with plasma-derived C1-inhibitor concentrate in pediatric hereditaryangioedema patients
909
Henriette Farkas, MD, PhD, DSc, Dorottya Csuka, MSc, Zsuzsanna Zotter, MD, Erika Szabo, MD, Ibolya Czaller, MD,Lilian Varga, PhD, Janos Fejes, MD, George Fust, PhD, DSc, and George Harmat, MD, PhD, Budapest, Hungary
This follow-up study evaluated 152 attacks in 42 pediatric patients with hereditary angioedema due to
C1-inhibitor deficiency. The study demonstrated that human plasma–derived C1-inhibitor concentrate is
effective and safe for the treatment of edematous attacks, regardless of location.
Continued on page 26A
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Effect of inhaled endotoxin on regional particle deposition in patients with mild asthma
912 William D. Bennett, PhD, Margaret Herbst, RN, Kirby L. Zeman, PhD, Jihong Wu, MD, Michelle L. Hernandez, MD, andDavid B. Peden, MD, Chapel Hill, NCEndotoxin causes an increased response to allergen in allergic asthmatic patients. The authors show that
inhalation of LPS modulates particle deposition in asthmatic but not healthy volunteers. This response might
account for the increased response to inhaled allergen caused by LPS exposure.
IL-33 is expressed in epithelia from patients with cystic fibrosis and potentiates neutrophilrecruitment
913
Lucie Roussel, PhD, Raquel Farias, MD, and Simon Rousseau, PhD, Montreal, Quebec, Canada
IL-33 is found in the nuclei of airway epithelial cells from patients with cystic fibrosis, and its expression is
induced by Pseudomonas aeruginosa diffusible material. IL-33, although not directly chemotactic for
neutrophils, potentiates their recruitment by bacteria-induced epithelial cell–derived chemoattractants.
Influence of heredity on asthma continues to adulthood
916 Taina K. Lajunen, PhD, Jouni J. K. Jaakkola, MD, DSc, PhD, and Maritta S. Jaakkola, MD, PhD, Oulu, FinlandThe results provide new evidence that the presence of asthma among both parents and siblings, as well as
children, conveys the clinician important information on the probability of adult-onset asthma, and asking
about it will aid the diagnostic procedure.
Relationships between folate and inflammatory features of asthma
918 Jenny H. Lin, MD, William Matsui, MD, Charles Aloe, MPH, Roger D. Peng, PhD, Gregory B. Diette, MD, MHS,Patrick N. Breysse, PhD, and Elizabeth C. Matsui, MD, MHS, Baltimore, MdThis study of urban asthmatic children found “bell-shaped” relationships between folate and allergic
inflammatory markers, suggesting that folate may modulate allergic inflammatory markers. Confirmation of
these findings would support clinical trials of folic acid supplementation.
Tolerance to wheat in whole-grain cereal biscuit in wheat-allergic children
920 Paul J. Turner, FRACP, PhD, Melanie Wong, FRACP, PhD, Nirupama Varese, MSc, Jennifer M. Rolland, PhD,Robyn E. O’Hehir, FRACP, PhD, and Dianne E. Campbell, FRACP, PhD, Sydney and Melbourne, AustraliaThis study reports 2 children with confirmed wheat allergy who could tolerate whole-grain wheat cereal
biscuits. To our knowledge, this is the first report of wheat-allergic patients tolerating modified wheat.
Initial description of pork-cat syndrome in the United States
923 Jonathon Posthumus, MD, Hayley R. James, BS, Charles J. Lane, MD, Luis A. Matos, MD, Thomas A. E. Platts-Mills, MD, PhD, FRS,and Scott P. Commins, MD, PhD, Charlottesville and Lynchburg, VaThe authors report an initial identification of 8 patients in the United States with pork-cat syndrome, an
uncommon food allergy to pork resulting from sensitization to cat serum albumin.
Correspondence
Interferon regulatory factor 3 activation mediates viral stimulus-induced bronchialproduction of thymic stromal lymphopoietin
926
Lena Uller, PhD, Lund, Sweden
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Contin
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J ALLERGY
Reply
926 Steven F. Ziegler, PhD, Seattle, WashAbsence of homogenization might explain the benefits of raw cow’s milk
927 Jeffrey D. Miller, MD, Hawleyville, ConnReply
927 R. J. Joost van Neerven, PhD, Edward F. Knol, PhD, Jeroen M. L. Heck, PhD, and Huub F. J. Savelkoul, PhD, Wageningen, Amersfoort,and Utrecht, The NetherlandsRole of neurokinin-1 receptor in patients with artemin-induced warmth-provoked pruritus
928 Shawn G. Kwatra, MD, Chicago, IllReply
928 Hiroyuki Murota, MD, PhD, and Ichiro Katayama, MD, PhD, Osaka, JapanReader services
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751uing Medical Education (CME) credit is available to readers who successfully complete examinations accompanying the article
nthlyClinical Reviews in Allergy and Immunology series. In addition, CME andMaintenance of Certification credit are available
ccessful completion of examinations accompanying articles in the monthlyMaintenance of Certification Clinical Managementese opportunities further the joint educational goals of the Journal and its sponsoring foundation, the American Academy of
sthma & Immunology (AAAAI). Learning objectives and full details appear in these articles in the print and online Journal. The
ted examinations can be taken at the JACI Web site (www.jacionline.org). Credit is administered by the AAAAI.
opinions expressed in the articles and communications herein are those of the author(s) and not necessarily those of the Editor, publisher, or the American Academy ofa & Immunology. The Editor, publisher, and the American Academy of Allergy, Asthma & Immunology disclaim any responsibility or liability for such material ande, warrant, or endorse any product or service advertised in this publication, nor do they guarantee any claim made by the manufacturer of such product or service.
CLIN IMMUNOL March 2013 29A
