Publications by authors named "Jonathan Parsons"

64 Publications

Exercise-induced bronchoconstriction update-2016.

J Allergy Clin Immunol 2016 11 21;138(5):1292-1295.e36. Epub 2016 Sep 21.

The first practice parameter on exercise-induced bronchoconstriction (EIB) was published in 2010. This updated practice parameter was prepared 5 years later. In the ensuing years, there has been increased understanding of the pathogenesis of EIB and improved diagnosis of this disorder by using objective testing. At the time of this publication, observations included the following: dry powder mannitol for inhalation as a bronchial provocation test is FDA approved however not currently available in the United States; if baseline pulmonary function test results are normal to near normal (before and after bronchodilator) in a person with suspected EIB, then further testing should be performed by using standardized exercise challenge or eucapnic voluntary hyperpnea (EVH); and the efficacy of nonpharmaceutical interventions (omega-3 fatty acids) has been challenged. The workgroup preparing this practice parameter updated contemporary practice guidelines based on a current systematic literature review. The group obtained supplementary literature and consensus expert opinions when the published literature was insufficient. A search of the medical literature on PubMed was conducted, and search terms included pathogenesis, diagnosis, differential diagnosis, and therapy (both pharmaceutical and nonpharmaceutical) of exercise-induced bronchoconstriction or exercise-induced asthma (which is no longer a preferred term); asthma; and exercise and asthma. References assessed as relevant to the topic were evaluated to search for additional relevant references. Published clinical studies were appraised by category of evidence and used to document the strength of the recommendation. The parameter was then evaluated by Joint Task Force reviewers and then by reviewers assigned by the parent organizations, as well as the general membership. Based on this process, the parameter can be characterized as an evidence- and consensus-based document.
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http://dx.doi.org/10.1016/j.jaci.2016.05.029DOI Listing
November 2016

Differential effects of 10-Hz and 40-Hz transcranial alternating current stimulation (tACS) on endogenous versus exogenous attention.

Cogn Neurosci 2017 04 14;8(2):102-111. Epub 2016 Jun 14.

b Departments of Psychiatry, Cell Biology and Physiology, Biomedical Engineering, and Neurology , University of North Carolina , Chapel Hill , NC , USA.

Previous electrophysiological studies implicate both alpha (8-12 Hz) and gamma (>30 Hz) neural oscillations in the mechanisms of selective attention. Here, participants preformed two separate visual attention tasks, one endogenous and one exogenous, while transcranial alternating current stimulation (tACS), at 10 Hz, 40 Hz, or sham, was applied to the right parietal lobe. Our results provide new evidence for the roles of gamma and alpha oscillations in voluntary versus involuntary shifts of attention. Gamma (40 Hz) stimulation resulted in improved disengagement from invalidly cued targets in the endogenous attention task, whereas alpha stimulation (10 Hz) had no effect on endogenous attention, but increased the exogenous cuing effect. These findings agree with previous studies suggesting that right inferior parietal regions may be especially important for the disengagement of attention, and go further to provide details about the specific type of oscillatory neural activity within that brain region that is differentially involved in endogenous versus exogenous attention. Our results also have potential implications for the plasticity and training of attention systems.
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http://dx.doi.org/10.1080/17588928.2016.1194261DOI Listing
April 2017

Eucapnic Voluntary Hyperventilation to Detect Exercise-Induced Bronchoconstriction in Cystic Fibrosis.

Lung 2015 Oct 3;193(5):733-8. Epub 2015 Jun 3.

Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus, OH, USA.

Background: Exercise-induced bronchoconstriction (EIB) has not been well studied in cystic fibrosis (CF), and eucapnic voluntary hyperventilation (EVH) testing has not been used as an objective assessment of EIB in CF to date.

Methods: A prospective cohort pilot study was completed where standard EVH testing was completed by 10 CF patients with forced expiratory volume in 1 s (FEV1) ≥70% of predicted. All patients also completed a cardiopulmonary exercise test (CPET) with pre- and post-CPET spirometry as a comparative method of detecting EIB.

Results: No adverse events occurred with EVH testing. A total of 20% (2/10) patients were diagnosed with EIB by means of EVH. Both patients had clinical symptoms consistent with EIB. No patient had a CPET-based exercise challenge consistent with EIB.

Conclusions: EVH testing was safe and effective in the objective assessment for EIB in patients with CF who had well-preserved lung function. It may be a more sensitive method of detecting EIB then exercise challenge.
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http://dx.doi.org/10.1007/s00408-015-9745-3DOI Listing
October 2015

Exercise-induced bronchoconstriction.

Ann Am Thorac Soc 2014 Dec;11(10):1651-2

1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, California.

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http://dx.doi.org/10.1513/AnnalsATS.201409-427OTDOI Listing
December 2014

Improving screening and diagnosis of exercise-induced bronchoconstriction: a call to action.

J Allergy Clin Immunol Pract 2014 May-Jun;2(3):275-80.e7. Epub 2014 Feb 4.

BioMedEcon, LLC, Moss Beach, Calif.

This article summarizes the findings of an expert panel of nationally recognized allergists and pulmonologists who met to discuss how to improve detection and diagnosis of exercise-induced bronchoconstriction (EIB), a transient airway narrowing that occurs during and most often after exercise in people with and without underlying asthma. EIB is both commonly underdiagnosed and overdiagnosed. EIB underdiagnosis may result in habitual avoidance of sports and physical activity, chronic deconditioning, weight gain, poor asthma control, low self-esteem, and reduced quality of life. Routine use of a reliable and valid self-administered EIB screening questionnaire by professionals best positioned to screen large numbers of people could substantially improve the detection of EIB. The authors conducted a systematic review of the literature that evaluated the accuracy of EIB screening questionnaires that might be adopted for widespread EIB screening in the general population. Results of this review indicated that no existing EIB screening questionnaire had adequate sensitivity and specificity for this purpose. The authors present a call to action to develop a new EIB screening questionnaire, and discuss the rigorous qualitative and quantitative research necessary to develop and validate such an instrument, including key methodological pitfalls that must be avoided.
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http://dx.doi.org/10.1016/j.jaip.2013.11.001DOI Listing
January 2015

Exercise-induced bronchoconstriction.

Otolaryngol Clin North Am 2014 Feb 5;47(1):119-26. Epub 2013 Oct 5.

Wexner Medical Center, The Ohio State University, 201 Davis Heart/Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210, USA. Electronic address:

Exercise-induced bronchoconstriction (EIB) occurs commonly in patients with asthma but also can affect individuals without asthma. EIB is particularly common in populations of athletes. Common symptoms include cough, dyspnea, chest tightness, and wheezing; however, there can be a variety of more subtle symptoms. In this article, the clinical presentation of EIB as well as the diagnosis and treatment of EIB are outlined.
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http://dx.doi.org/10.1016/j.otc.2013.09.003DOI Listing
February 2014

Sex differences in asthma symptom profiles and control in the American Lung Association Asthma Clinical Research Centers.

Respir Med 2013 Oct 21;107(10):1491-500. Epub 2013 Aug 21.

Wexner Medical Center at The Ohio State University, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, 201 Davis Heart & Lung Research Institute, 473 W. 12th Avenue, Columbus, OH 43210, USA. Electronic address:

Objective: Important differences between men and women with asthma have been demonstrated, with women describing more symptoms and worse asthma-related quality of life (QOL) despite having similar or better pulmonary function. While current guidelines focus heavily on assessing asthma control, they lack information about whether sex-specific approaches to asthma assessment should be considered. We sought to determine if sex differences in asthma control or symptom profiles exist in the well-characterized population of participants in the American Lung Association Asthma Clinical Research Centers (ALA-ACRC) trials.

Methods: We reviewed baseline data from four trials published by the ALA-ACRC to evaluate individual item responses to three standardized asthma questionnaires: the Juniper Asthma Control Questionnaire (ACQ), the multi-attribute Asthma Symptom Utility Index (ASUI), and Juniper Mini Asthma Quality of Life Questionnaire (mini-AQLQ).

Results: In the poorly-controlled population, women reported similar overall asthma control (mean ACQ 1.9 vs. 1.8; p = 0.54), but were more likely to report specific symptoms such as nocturnal awakenings, activity limitations, and shortness of breath on individual item responses. Women reported worse asthma-related QOL on the mini-AQLQ (mean 4.5 vs. 4.9; p < 0.001) and more asthma-related symptoms with a lower mean score on the ASUI (0.73 vs. 0.77; p ≤ 0.0001) and were more likely to report feeling bothered by particular symptoms such as coughing, or environmental triggers.

Conclusions: In participants with poorly-controlled asthma, women had outwardly similar asthma control, but had unique symptom profiles on detailed item analyses which were evident on evaluation of three standardized asthma questionnaires.
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http://dx.doi.org/10.1016/j.rmed.2013.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816372PMC
October 2013

Exercise-induced bronchospasm, asthma control, and obesity.

Allergy Asthma Proc 2013 Jul-Aug;34(4):342-8

Allergy and Asthma Medical Group and Reasearch Center, San Diego, CA, USA.

Exercise-induced bronchospasm (EIB) commonly affects patients with asthma. However, the relationship between EIB and asthma control remains unclear. Exercise limitation due to asthma might lead to reduced physical activity, but little information is available regarding obesity and EIB in asthma. A recent survey evaluated the frequency of EIB and exercise-related respiratory symptoms in a large number of patients with asthma. The survey results were reanalyzed to address any relationship between EIB and asthma control and obesity. A nationwide random sample of children aged 4-12 years (n = 250), adolescents aged 13-17 years (n = 266), and adults aged ≥18 years (n = 1001) with asthma were interviewed by telephone. Questions in the survey addressed asthma symptoms in general, medication use, and height and weight. Asthma control was categorized using established methods in the Expert Panel Report 3. Body mass index (BMI) was calculated using standard nomograms and obesity was defined as a BMI ≥ 30 kg/m(2). Most children (77.6%), adolescents (71.1%), and adults (83.1%) had either "not well" or "very poorly" controlled asthma. Children with "not well" controlled asthma reported a history of EIB significantly more often than those with "well" controlled" asthma. Asthma patients of all ages who had "not well" and "very poorly" controlled asthma described multiple (four or more) exercise-related respiratory symptoms significantly more often than those with "well-controlled" asthma. Obesity was significantly more common in adolescents with "not well" and "very poorly" controlled asthma and adults with "very poorly" controlled asthma. Children, adolescents, and adults with asthma infrequently have well-controlled disease. A history of EIB and exercise-related respiratory symptoms occur more commonly in patients with not well and very poorly controlled asthma. Obesity was found more often in adolescents and adults, but not children, with asthma, which was not well and very poorly controlled.
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http://dx.doi.org/10.2500/aap.2013.34.3674DOI Listing
October 2013

Low-frequency intermediate penetrance variants in the ROCK1 gene predispose to Tetralogy of Fallot.

BMC Genet 2013 Jun 19;14:57. Epub 2013 Jun 19.

Institute of Genetic Medicine, Newcastle University, Newcastle, UK.

Background: Epidemiological studies indicate a substantial excess familial recurrence of non-syndromic Tetralogy of Fallot (TOF), implicating genetic factors that remain largely unknown. The Rho induced kinase 1 gene (ROCK1) is a key component of the planar cell polarity signalling pathway, which plays an important role in normal cardiac development. The aim of this study was to investigate the role of genetic variation in ROCK1 on the risk of TOF.

Results: ROCK1 was sequenced in a discovery cohort of 93 non-syndromic TOF probands to identify rare variants. TagSNPs were selected to capture commoner variation in ROCK1. Novel variants and TagSNPs were genotyped in a discovery cohort of 458 TOF cases and 1331 healthy controls, and positive findings were replicated in a further 209 TOF cases and 1290 healthy controls. Association between genotypes and TOF was assessed using LAMP.A rare SNP (c.807C > T; rs56085230) discovered by sequencing was associated with TOF risk (p = 0.006) in the discovery cohort. The variant was also significantly associated with the risk of TOF in the replication cohort (p = 0.018). In the combined cohorts the odds ratio for TOF was 2.61 (95% CI 1.58-4.30); p < 0.0001. The minor allele frequency of rs56085230 in the cases was 0.02, and in the controls it was 0.007. The variant accounted for 1% of the population attributable risk (PAR) of TOF. We also found significant association with TOF for an uncommon TagSNP in ROCK1, rs288979 (OR 1.64 [95% CI 1.15-2.30]; p = 1.5x10⁻⁵). The minor allele frequency of rs288979 in the controls was 0.043, and the variant accounted for 11% of the PAR of TOF. These association signals were independent of each other, providing additional internal validation of our result.

Conclusions: Low frequency intermediate penetrance (LFIP) variants in the ROCK1 gene predispose to the risk of TOF.
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http://dx.doi.org/10.1186/1471-2156-14-57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734041PMC
June 2013

An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction.

Am J Respir Crit Care Med 2013 May;187(9):1016-27

Background: Exercise-induced bronchoconstriction (EIB) describes acute airway narrowing that occurs as a result of exercise. EIB occurs in a substantial proportion of patients with asthma, but may also occur in individuals without known asthma.

Methods: To provide clinicians with practical guidance, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB and to develop evidence-based guidelines for the diagnosis and treatment of EIB. The evidence was appraised and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.

Results: Recommendations for the treatment of EIB were developed. The quality of evidence supporting the recommendations was variable, ranging from low to high. A strong recommendation was made for using a short-acting β(2)-agonist before exercise in all patients with EIB. For patients who continue to have symptoms of EIB despite the administration of a short-acting β(2)-agonist before exercise, strong recommendations were made for a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise.

Conclusions: The recommendations in this Guideline reflect the currently available evidence. New clinical research data will necessitate a revision and update in the future.
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http://dx.doi.org/10.1164/rccm.201303-0437STDOI Listing
May 2013

Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.

Hum Mol Genet 2013 Apr 7;22(7):1473-81. Epub 2013 Jan 7.

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10(-7)) and replicated convincingly (P = 3.9 × 10(-5)) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10(-11) in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10(-7)) and replicated convincingly (P = 1.2 × 10(-5)) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10(-11) in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF.
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http://dx.doi.org/10.1093/hmg/dds552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596849PMC
April 2013

Managing respiratory problems in athletes.

Clin Med (Lond) 2012 Aug;12(4):351-6

Centre for Clinical Pharmacology, Division of Biomedical Sciences, St George's, University of London, London.

Respiratory problems are common in athletes of all abilities and can significantly impact upon their health and performance. In this article, we provide an overview of respiratory physiology in athletes. We also discuss the assessment and management of common clinical respiratory conditions as they pertain to athletes, including airways disease, respiratory tract infection and pneumothorax. We focus on providing a pragmatic approach and highlight important caveats for the physician treating respiratory conditions in this highly specific population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4952126PMC
http://dx.doi.org/10.7861/clinmedicine.12-4-351DOI Listing
August 2012

Etiology of dyspnea in elite and recreational athletes.

Phys Sportsmed 2012 May;40(2):28-33

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.

Background: Breathing complaints are common in athletes. Studies have suggested that the prevalence of asthma and exercise-induced bronchoconstriction (EIB) is higher in elite athletes than the general population. Vocal cord dysfunction (VCD) may mimic asthma and EIB as a cause of dyspnea in athletes. However, the majority of studies to date have primarily relied on symptoms to diagnose VCD, and there are limited data on coexistence of asthma, EIB, and/or VCD. It is well established that symptoms alone are inadequate to accurately diagnose EIB and VCD. Our goal was to define via objective testing the prevalence of asthma, EIB, VCD alone, or in combination in a cohort of athletes with respiratory complaints.

Methods: A retrospective chart review was done of 148 consecutive athletes (collegiate, middle school, high school, and recreational) referred to a tertiary care center's asthma center for evaluation of respiratory complaints with exercise. An evaluation including medical history, physical examination, and objective testing including pulmonary function testing (PFT), eucapnic voluntary hyperventilation, and video laryngostroboscopy, were performed.

Results: The most common symptom was dyspnea on exertion (96%), with < 1% complaining of either hoarseness or stridor. The most common diagnosis prior to referral was asthma (40%). Only 16% had PFTs prior to referral. Following evaluation by a pulmonologist, 52% were diagnosed with EIB, 17% with asthma, and 70% with VCD. Of those diagnosed with asthma before our evaluation, the diagnosis of asthma was confirmed, with PFTs in only 19 of 59 (32%) athletes based on our testing. Vocal cord dysfunction was more common in females and in adolescent athletes. Coexistence of multiple disorders was common, such as EIB and asthma (8%), EIB and VCD (31%), and VCD and asthma (6%).

Conclusions: Asthma and EIB are common etiologies of dyspnea in athletes, both competitive and recreational. However, VCD is also common and can coexist with either asthma or EIB. Vocal cord dysfunction may contribute to exercise-related respiratory symptoms more frequently in middle school- and high school-aged athletes than in college athletes. Effective treatment of dyspnea requires appropriate identification and treatment of all disorders. Classic symptoms of stridor and/or hoarseness are often not present in athletes with VCD. Accurate diagnosis of asthma, EIB, and VCD requires objective testing and can prevent exposure of patients to medications that are ineffective and have potential adverse side effects. Furthermore, there is need for increased awareness of VCD as a common cause of respiratory complaints in athletes, either as a single diagnosis or in combination with EIB, especially in females, as well as middle school and high school athletes.
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http://dx.doi.org/10.3810/psm.2012.05.1962DOI Listing
May 2012

Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part I: aminoalkoxypyrimidine carboxamides.

Bioorg Med Chem Lett 2012 Jun 17;22(11):3693-8. Epub 2012 Apr 17.

Vertex Pharmaceuticals, Inc., 130 Waverly St., Cambridge, MA 02139, United States.

A series of 2,6-disubstituted aminoalkoxypyrimidine carboxamides (AAPCs) with potent inhibition of bacterial NAD(+)-dependent DNA ligase was discovered through the use of structure-guided design. Two subsites in the NAD(+)-binding pocket were explored to modulate enzyme inhibitory potency: a hydrophobic selectivity region was explored through a series of 2-alkoxy substituents while the sugar (ribose) binding region of NAD(+) was explored via 6-alkoxy substituents.
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http://dx.doi.org/10.1016/j.bmcl.2012.04.037DOI Listing
June 2012

Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part 2: 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones.

Bioorg Med Chem Lett 2012 Jun 19;22(11):3699-703. Epub 2012 Apr 19.

Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, United States.

A series of 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones were designed and synthesized as a novel class of inhibitors of NAD(+)-dependent DNA ligase that possess potency against Gram-positive bacteria.
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http://dx.doi.org/10.1016/j.bmcl.2012.04.038DOI Listing
June 2012

A common variant in the PTPN11 gene contributes to the risk of tetralogy of Fallot.

Circ Cardiovasc Genet 2012 Jun 13;5(3):287-92. Epub 2012 Apr 13.

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

Background: Tetralogy of Fallot (TOF) is the commonest cyanotic form of congenital heart disease. In 80% of cases, TOF behaves as a complex genetic condition exhibiting significant heritability. As yet, no common genetic variants influencing TOF risk have been robustly identified.

Methods And Results: Two hundred and seven haplotype-tagging single nucleotide polymorphisms in 22 candidate genes were genotyped in a test cohort comprising 362 nonsyndromic British white patients with TOF together with 717 unaffected parents of patients and 183 unrelated healthy controls. Single nucleotide polymorphisms with suggestive evidence of association in the test cohort (P<0.01) were taken forward for genotyping in an independent replication cohort comprising 392 cases of TOF, 218 unaffected parents of patients, and 1319 controls. Significant association was observed for 1 single nucleotide polymorphism, rs11066320 in the PTPN11 gene, in both the test and the replication cohort. Genotype at rs11066320 was associated with a per-allele odds ratio of 1.34 (95% confidence interval [CI], 1.19 to 1.52; P=2.9 × 10(-6)) in the total cohort of TOF cases and controls; this remained highly significant after Bonferroni correction for 207 analyses (corrected P=0.00061). Genotype at rs11066320 was responsible for a population-attributable risk of TOF of approximately 10%.

Conclusions: Common variation in the linkage disequilibrium block including the PTPN11 gene contributes to the risk of nonsyndromic TOF. Rare mutations in PTPN11 are known to cause the autosomal dominant condition Noonan syndrome, which includes congenital heart disease, by upregulating Ras/mitogen-activated protein kinase (MAPK) signaling. Our results suggest a role for milder perturbations in PTPN11 function in sporadic, nonsyndromic congenital heart disease.
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http://dx.doi.org/10.1161/CIRCGENETICS.111.962035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643453PMC
June 2012

HIV and asthma, is there an association?

Respir Med 2012 Apr 27;106(4):493-9. Epub 2012 Jan 27.

The Ohio State University, Department of Internal Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, 201 Davis Heart & Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210, USA.

Objective: To evaluate whether asthma and airway hyper-responsiveness are associated with HIV infection.

Methods: We reviewed the literature on HIV-associated pulmonary diseases, pulmonary symptoms, and immune changes which may play a role in asthma. The information was analyzed comparing the pre-HAART era to the post-HAART era data.

Results: HIV-seropositive individuals commonly experience respiratory complaints yet it is unclear if the frequency of these complaints have changed with the initiation of HAART. Changes in pulmonary function testing and serum IgE are seen with HIV infection even in the post-HAART era. An increased prevalence of asthma among HIV-seropositive children treated with HAART has been reported.

Conclusion: The spectrum of HIV-associated pulmonary disease has changed with the introduction of HAART. Current data is limited to determine if asthma and airway hyper-responsiveness are more common among HIV-seropositive individuals treated with HAART.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235227PMC
http://dx.doi.org/10.1016/j.rmed.2011.12.017DOI Listing
April 2012

Screening for exercise-induced bronchoconstriction in college athletes.

J Asthma 2012 Mar 25;49(2):153-7. Epub 2012 Jan 25.

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, The Ohio State University Medical Center, Columbus, OH, USA.

Objective: Previous studies have reported that the prevalence of exercise-induced bronchoconstriction (EIB) in athletes is higher than that of the general population. There is increasing evidence that athletes fail to recognize and report symptoms of EIB. As a result, there has been debate whether athletes should be screened for EIB, particularly in high-risk sports.

Methods: We prospectively studied 144 athletes from six different varsity sports at a large National Collegiate Athletic Association Division I collegiate athletic program. Baseline demographics and medical history were obtained and the presence of asthma symptoms during exercise was documented. Each athlete subsequently underwent a eucapnic voluntary hyperventilation (EVH) test to document the presence of EIB. Exhaled nitric oxide (eNO) quantification was performed immediately before EVH testing. EIB was defined as a ≥10% decline in forced expiratory volume in 1 second compared with baseline.

Results: Only 4 of 144 (2.7%) athletes were EIB-positive after EVH testing. The presence of symptoms was not predictive of EIB as only 2 of the 64 symptomatic athletes (3%) were EIB-positive based on EVH testing. Two of the four athletes who were found to be EIB-positive denied such symptoms. The mean baseline eNO in the four EIB-positive athletes was 13.25 parts per billion (ppb) and 24.5 ppb in the EIB-negative athletes.

Conclusions: Our data argue that screening for EIB is not recommended given the surprisingly low prevalence of EIB in the population we studied. In addition, the presence or absence of symptoms was not predictive of EIB and eNO testing was not effective in predicting EIB.
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http://dx.doi.org/10.3109/02770903.2011.652329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832203PMC
March 2012

Exercise-induced bronchospasm: a case study in a nonasthmatic patient.

J Am Acad Nurse Pract 2012 Jan;24(1):19-23

University of Virginia, Charlottesville, Virginia 22908, USA.

Purpose: To provide an overview of the clinical presentation, diagnosis, and management of exercise-induced bronchospasm (EIB) without underlying asthma.

Data Sources: Case presentation and review of the EIB Landmark Survey.

Conclusions: EIB is a common and well-described occurrence in patients with asthma, as well as in patients with no overt respiratory condition. Treatment with a short-acting beta-agonist before starting exercise is effective, yet this treatment approach is underutilized in the majority of patients with asthma.

Implications For Practice: This case highlights the implications of undermanaged EIB and the disconnect between healthcare provider recommendations and the beliefs and behaviors in patients with EIB. Inhaled short-acting beta-agonists can attenuate EIB in 80%-95% of patients and are effective during 2-3 h of exercise. Patients with a compromised level of physical activity because of EIB who do not respond to conventional treatment strategies should be referred to a respiratory specialist for diagnostic evaluation and confirmation of underlying asthma. Nurse practitioners should remain vigilant to identify untreated EIB and ensure that affected patients understand the condition and appropriate treatment options.
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http://dx.doi.org/10.1111/j.1745-7599.2011.00691.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378720PMC
January 2012

Impact of exercise-related respiratory symptoms in adults with asthma: Exercise-Induced Bronchospasm Landmark National Survey.

Allergy Asthma Proc 2011 Nov-Dec;32(6):431-7

Department of Pulmonary, Allergy, Critical Care, and Sleep Disorders, Ohio State University Asthma Center, Columbus, 34210, USA.

An estimated 5-20% of the general population and up to 90% of people with asthma experience exercise-induced bronchospasm (EIB). The EIB Landmark Survey is the first comprehensive study on exercise-related respiratory symptoms in the United States. Two surveys were conducted: the first surveyed adults (≥18 years) in the general public and the second surveyed adults with asthma or taking medications for asthma in the prior year. Parameters assessed included exercise-related respiratory symptoms, activity levels, and short-acting beta-antagonist (SABA) use. In the general public survey (n = 1085), 8% were currently diagnosed with asthma. However, 29% reported experiencing one or more of six respiratory-related symptoms during or immediately after exercising. In the EIB in adult asthma survey (n = 1001), although >80% of adults experienced one or more of six exercise-related respiratory symptoms, only 30.6% reported a diagnosis of EIB. Almost one-half (45.6%) of adults with asthma reported that they avoid physical activities because of symptoms. Despite symptoms, only 22.2% of respondents took SABAs before exercise "always" or "most of the time"; 36.3% took rescue medications after or during exercise. Exercise-related respiratory symptoms limit physical activities and negatively impact daily lives. However, adults in the United States lack awareness of EIB. Although many subjects stated that their asthma symptoms limit their physical activity, few adhered to treatment guidelines by using SABAs appropriately before exercising. Findings from this survey support the need for better communication about the proper evaluation and management of EIB in the community and in asthma patients.
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http://dx.doi.org/10.2500/aap.2011.32.3501DOI Listing
May 2012

Exercise-induced bronchospasm in children with asthma in the United States: results from the Exercise-Induced Bronchospasm Landmark Survey.

Allergy Asthma Proc 2011 Nov-Dec;32(6):425-30

Allergy and Asthma Medical Group and Research Center, San Diego, California 92123, USA.

Despite the availability of effective therapies, uncontrolled asthma remains a common problem. Previous large surveys suggest that exercise-related respiratory symptoms may be a significant element of uncontrolled asthma. The Exercise-Induced Bronchospasm (EIB) Landmark Survey is the first comprehensive, national survey evaluating EIB awareness and impact among the general public, asthma patients, and health care providers. This study was designed to evaluate the prevalence and impact of exercise-related respiratory symptoms in children (aged 4-17 years) with asthma. A national survey was conducted with parents of 516 children diagnosed with asthma or taking medications for asthma in the prior year. The majority of parents reported that their child experienced one or more exercise-related respiratory symptom and almost one-half (47.4%) experienced four or more symptoms. Most commonly reported symptoms were coughing, shortness of breath, and wheezing. Respondents reported that asthma limited their child's ability to participate either "a lot" or "some" in sports (30%), other outdoor activities (26.3%), and normal physical exertion (20.9%). Only 23.1% of children with exercise-related respiratory symptoms were reported to take short-acting beta-agonists such as albuterol "always" or "most of the time" before exercising. Exercise-related respiratory symptoms among pediatric asthma patients are common and substantially limit the ability of children to participate normally and perform optimally in physical activities. Such symptoms may reflect uncontrolled underlying asthma that should be evaluated and treated with appropriate controller medications. Despite the availability of preventative therapy, many children do not use short-acting bronchodilators before exercise as recommended in national guidelines.
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http://dx.doi.org/10.2500/aap.2011.32.3502DOI Listing
May 2012

Exercise-induced bronchospasm: implications for patients with or without asthma in primary care practice.

Int J Gen Med 2011 18;4:779-82. Epub 2011 Nov 18.

University of Nevada School of Medicine, Reno, NV.

Exercise-induced bronchospasm (EIB) can represent a substantial barrier to physical activity. We present the cases of two patients with EIB, one with asthma, and one without asthma, who were evaluated at our primary care practice. The first case was a 44-year-old man with a history of seasonal allergic rhinitis but no asthma, who reported difficulty breathing when playing tennis. The second case was a 45-year-old woman who presented with persistent, generally well-controlled asthma, who was now experiencing bouts of coughing and wheezing during exercise. In both cases, an exercise challenge was used to diagnose EIB, and patients were prescribed a short-acting beta agonist to be used immediately before initiating exercise. EIB is a frequently encountered problem among patients presenting to primary care specialists. Affected patients should be made aware of the importance of proactive treatment with a short-acting beta agonist before initiating any exercise.
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http://dx.doi.org/10.2147/IJGM.S20327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233371PMC
October 2012

Vocal cord dysfunction and asthma.

Curr Opin Pulm Med 2011 Jan;17(1):45-9

Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, The Ohio State University Medical Center, Columbus, Ohio, USA.

Purpose Of Review: Vocal cord dysfunction can occur independently or can co-exist with asthma. It often mimics asthma in presentation and can be challenging to diagnose, particularly in those with known asthma. Vocal cord dysfunction remains under-recognized, which may result in unnecessary adjustments to asthma medicines and increased patient morbidity. There is a need to review current literature to explore current theories regarding disease presentation, diagnosis, and treatment.

Recent Findings: The underlying cause of vocal cord dysfunction is likely multifactorial but there has been increased interest in hyper-responsiveness of the larynx. Many intrinsic and extrinsic triggers have been identified which in part may explain asthma-like symptomatology. A variety of techniques have been reported to provoke vocal cord dysfunction during testing which may improve diagnosis. There is a significant gap in the literature regarding specific laryngeal control techniques, duration of therapy, and the effectiveness of laryngeal control as a treatment modality.

Summary: Those with vocal cord dysfunction and asthma report more symptoms on standardized asthma control questionnaires, which can result in increasing amounts of medication if vocal cord dysfunction is not identified and managed appropriately. Clinicians need to maintain a high index of suspicion to identify these patients. Videolaryngostroboscopy remains the diagnostic method of choice. Evidence-based guidelines are needed for the most effective diagnostic techniques. Laryngeal control taught by speech pathologists is the most common treatment. Effectiveness is supported in case reports and clinical experience, but not in larger randomized trials which are needed.
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http://dx.doi.org/10.1097/MCP.0b013e32834130eeDOI Listing
January 2011

Current concepts in the diagnosis and management of exercise-induced bronchospasm.

Phys Sportsmed 2010 Dec;38(4):48-53

The Ohio State University Medical Center, Ohio State University Asthma Center, Columbus, OH, USA.

Exercise-induced bronchospasm (EIB) is a common occurrence in individuals with asthma, though it can also affect individuals without asthma. It occurs frequently in athletes. Common symptoms include coughing, dyspnea, chest tightness, and wheezing; however, there can be a variety of more subtle symptoms. The differential diagnosis of EIB is broad and includes several pulmonary and cardiac disorders. During the initial evaluation, a complete history, physical examination, and spirometry should be performed. In most patients with EIB, the baseline spirometry is normal; therefore, bronchoprovocation testing is strongly recommended. Both pharmacologic and nonpharmacologic approaches are important in the treatment of EIB. Management of EIB on the sideline of athletic events requires preparation and immediate access to rescue inhalers.
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http://dx.doi.org/10.3810/psm.2010.12.1824DOI Listing
December 2010

Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants.

Heart 2010 Oct;96(20):1651-5

Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK.

Background: Tetralogy of Fallot (TOF) is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor TBX1.

Objective: To assess the contribution of common and rare TBX1 genetic variants to TOF.

Design: Rare TBX1 variants were sought by resequencing coding exons and splice-site boundaries. Common TBX1 variants were investigated by genotyping 20 haplotype-tagging SNPs capturing all the common variations present at the locus. Association analysis was performed using the program UNPHASED.

Patients: TBX1 exons were sequenced in 93 patients with non-syndromic TOF. Single nucleotide polymorphism analysis was performed in 356 patients with TOF, their parents and healthy controls.

Results: Three novel variants not present in 1000 chromosomes from healthy ethnically matched controls were identified. One of these variants, an in-frame 57 base-pair deletion in the third exon which removed 19 evolutionarily conserved residues, decreased transcriptional activity by 40% in a dual luciferase assay (p=0.008). Protein expression studies demonstrated that this mutation affected TBX1 protein stability. After correction for multiple comparisons, no significant associations between common genetic variants and TOF susceptibility were found.

Conclusion: This study demonstrates that rare TBX1 variants with functional consequences are present in a small proportion of non-syndromic TOF.
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http://dx.doi.org/10.1136/hrt.2010.200121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976076PMC
October 2010

The relationship between gastroesophageal reflux and asthma: an update.

Ther Adv Respir Dis 2011 Apr 6;5(2):143-50. Epub 2010 Oct 6.

The Ohio State University Medical Center, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Columbus, Ohio 43210, USA.

Asthma and gastroesophageal reflux disease (GERD) are both common conditions and, hence, they often coexist. However, asthmatics have been found to have a much greater prevalence of GERD symptoms than the general population. There remains debate regarding the underlying physiologic mechanism(s) of this relationship and whether treatment of GERD actually translates into improved asthma outcomes. Based on smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, current guidelines recommend a trial of GERD treatment for symptomatic asthmatics even without symptoms of GERD. However, recently a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton-pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. These data suggest empiric treatment of asymptomatic GERD in asthmatics is not a useful practice. This review article provides an overview of the epidemiology and pathophysiologic relationships between asthma and GERD as well as a summary of current data regarding links between treatment of GERD with asthma outcomes.
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http://dx.doi.org/10.1177/1753465810384606DOI Listing
April 2011

Exercise-induced bronchospasm: symptoms are not enough.

Expert Rev Clin Immunol 2009 Jul;5(4):357-9

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http://dx.doi.org/10.1586/eci.09.15DOI Listing
July 2009

The oral health of children considered very high risk for infective endocarditis.

Int J Paediatr Dent 2010 May;20(3):173-8

Division of Child Dental Health, Leeds Dental Institute, Leeds, UK.

Background: Children with previous experience of infective endocarditis or with prosthetic heart valve are considered at very high risk for infective endocarditis.

Aim: The aim of this study was to compare the dental health of a group of these children with a group of healthy controls and to determine parental awareness of the importance of good oral health.

Design: Oral examination was carried out in 28 children with previous infective endocarditis or a prosthetic heart valve to assess oral health. Findings were compared to a healthy control group of 28. Questionnaires were distributed to the parents to assess awareness of oral health.

Results: There was no significant difference in DMFT scores of study and control group (2.43 +/- 3.72 and 1.36 +/- 2.5 respectively) or in DMFT scores of study and control group (1.5 +/- 1.73 and 1.15 +/- 1.42 respectively), 36% of the study group had untreated caries. Parental knowledge of the link between oral health and infective endocarditis was excellent.

Conclusions: There were no significant differences between the oral health of cardiac children and healthy children although the dmft and DMFT scores of the study group were high. Of concern was the proportion of children with untreated caries in spite of good dental awareness and attendance.
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http://dx.doi.org/10.1111/j.1365-263X.2010.01034.xDOI Listing
May 2010

Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase.

Bioorg Med Chem Lett 2010 May 15;20(9):2828-31. Epub 2010 Mar 15.

Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA.

Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphylococcus aureus GyrB.
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http://dx.doi.org/10.1016/j.bmcl.2010.03.052DOI Listing
May 2010