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INTRODUCTION: Anti-inflammatory therapies are the mainstay for the treatment of inflammatory bowe... more INTRODUCTION:
Anti-inflammatory therapies are the mainstay for the treatment of inflammatory bowel disease (IBD) in children and adults, including biologics such as infliximab. While there is extensive literature on the general side effects of therapy with infliximab, the data on pulmonary adverse effects remains sparse. This article summarizes the literature related to pulmonary adverse effects of Infliximab therapy in Crohn's Disease.
AREA COVERED:
Published reports of specific pulmonary complications during ongoing therapy with infliximab in patients with IBD were included in the review. A wide variety of infectious and non-infectious complications have been reported with the use of infliximab therapy in IBD.
EXPERT OPINION:
It is important to carefully evaluate respiratory signs and symptoms in patients with IBD, especially those receiving biologic therapies. Besides infectious complications, other non-infectious pulmonary adverse effects associated with the use of infliximab should be considered in patients with IBD. Further, it is important to differentiate primary pulmonary involvement of IBD from pulmonary adverse effects of infliximab therapy. An algorithm for assessing patients with IBD presenting with pulmonary symptoms is provided as a guide for clinicians for medical decision-making.

INTRODUCTION: Pediatric lung abscesses can be primary or secondary, and there is limited data reg... more INTRODUCTION:
Pediatric lung abscesses can be primary or secondary, and there is limited data regarding response to treatments and patient outcomes.
OBJECTIVES:
To assess the clinical and microbiologic profile of pediatric patients with lung abscess and assess the differences in outcomes for patients treated with medical therapy or medical plus surgical therapy.
METHODS:
A retrospective review of all pediatric patients ≤ 18 years of age that were treated as an inpatient for lung abscess between the dates of August 2004 and August 2014 was conducted. Patients were divided into two subgroups based on the need for surgical intervention.
RESULTS:
A total of 39 patients with lung abscess (30 treated with medical therapy alone, 9 also required surgical interventions) were included. Fever, cough, and emesis were the most common presenting symptoms, and most of the patients had underlying respiratory (31%) or neurologic disorders (15%). Staphylococcus aureus was the most common organism in those that had culture results available, and ceftriaxone with clindamycin was the most common combination of antibiotics used for treatment. Comparison of medical and surgical subgroups identified the duration of fever and abscess size as risk factors for surgical intervention.
CONCLUSIONS:
Pediatric lung abscesses can be managed with medical therapy alone in most cases. Presence of prolonged duration of fever and larger abscess size may be predictive of the need for surgical intervention. Good clinical response to prolonged therapy with ceftriaxone and clindamycin was noted.

Mutations of the Surfactant Protein C (SPC) gene (SFTPC) have been associated with childhood inte... more Mutations of the Surfactant Protein C (SPC) gene (SFTPC) have been associated with childhood interstitial lung disease (chILD) with variable age of onset, severity of lung disease, and outcomes. We report a novel mutation in SFTPC [c.435G->A, p.(Gln145)] that was associated with onset of symptoms in early infancy, progressive respiratory failure with need for prolonged mechanical ventilatory support, and eventual lung transplant at 1 year of age. While the mutation was not predicted to alter the amino acid sequence of the SP-C precursor protein, analysis of SP-C transcripts demonstrated skipping of exon 4. Because of limited data about the outcomes of infants with SFTPC mutations, we conducted a systematic review of all the SFTPC mutations reported in the literature in order to define their presenting features, clinical and radiologic features, and outcomes. Further advances in our understanding of chILD and creation of an international registry will help to track these patients and their outcomes. Pediatr Pulmonol. 2016; 9999:XX–XX. ß 2016 Wiley Periodicals, Inc.

Since the first description of Cystic fibrosis (CF) more than 75 y ago, significant advances have... more Since the first description of Cystic fibrosis (CF) more than 75 y ago, significant advances have been made in understanding its pathogenesis and in developing specific therapies. The pace of these developments was further accelerated after the discovery of CF gene in 1989 and since then, CF has been transformed from being a pediatric illness into a chronic life-limiting genetic disorder with survival up to the fourth decade. The development of mutation-specific therapies in the first decade of the 21st century has the potential to change the natural history of CF and has now ushered in the era of 'Precision Medicine'. The ability to revert the basic defect in CF by using Personalized Medicine approach based on each individual's genetic profile will serve as a model for other chronic disorders as well. This review highlights the recent advances in the field of CF research that have led to a paradigm shift in its management and outcomes.

The Journal of …, Jan 1, 2011

Current Opinion in HIV and AIDS, Jan 1, 2010

Dengue Bulletin, Jan 1, 2005

BACKGROUND: As survival and outcomes continue to improve in neonates born prematurely, there is a... more BACKGROUND:
As survival and outcomes continue to improve in neonates born prematurely, there is an increasing need to promptly identify and treat pulmonary hypertension (PHT) in this population. Several echocardiographic indices have been used to evaluate for PHT. There is no clear consensus on how to utilize these parameters specifically for the evaluation of PHT in infants with chronic lung disease of prematurity.
OBJECTIVES:
Τhe objectives of the study were (1) to identify the different echocardiographic techniques for assessment of PHT in infants with chronic lung disease of prematurity in an evidence-based manner and (2) to establish an echocardiographic screening protocol based on available literature using different echocardiographic techniques.
METHODS:
We conducted a systematic review of the literature regarding use of echocardiographic techniques for evaluation of PHT in infants with bronchopulmonary dysplasia. On the basis of the available evidence, we came up with a screening algorithm using various echocardiographic techniques.
RESULTS:
We identified nine techniques that had been employed for detection of PHT noninvasively using echocardiography in 23 studies. Using these echocardiographic parameters, we came up with a flow chart to diagnose PHT in infants born prematurely, based on presence or absence of tricuspid regurgitation, presence or absence of patent ductus arteriosus, and direction of flow.
CONCLUSIONS:
We have proposed a new screening strategy for assessment of PHT using echocardiography in infants with chronic lung disease of prematurity. Further studies will be necessary to confirm its validity.

Pediatric Pulmonology, 2015

Idiopathic Nephrotic Syndrome (INS) has been believed to cause a false positive elevation of swea... more Idiopathic Nephrotic Syndrome (INS) has been believed to cause a false positive elevation of sweat chloride concentrations, as measured by the sweat test. Sweat tests were done for 11 children with acute onset INS at admission and again while they were in remission, with results being compared to normal historical controls. The initial sweat chloride concentration for 10 patients was normal (mean16.7 ± 11.02 mmol/L) and 1 patient had inadequate collection. This latter patient and two others were excluded during follow-up because of diagnoses other than INS. Sweat test results for the eight INS patients during follow up remained unchanged when they were in remission (16.94 ± 7.88 mmol/L; P = 0.98; Wilcoxon Matched-Pairs Signed Rank Test). In comparing sweat chloride concentrations from INS patients to those from 20 historical control subjects, we found no significant differences (Mann-Whitney Test; initial vs. control P = 0.643; follow up vs. control P = 0.806). INS does not cause a false positive sweat test. Further studies should be done to objectively assess the conditions that have been reported to affect sweat chloride concentrations. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.

International Journal of Health Care Quality Assurance, 2015

Annual screening for cystic fibrosis-related-diabetes (CFRD) using oral glucose tolerance test (O... more Annual screening for cystic fibrosis-related-diabetes (CFRD) using oral glucose tolerance test (OGTT) is recommended, but national testing rates are low. The purpose of this paper is to implement the quality improvement (QI) initiative to improve cystic fibrosis (CF) annual screening rates among patients at one CF center. To improve screening for CFRD at the CF Center, the authors used the Dartmouth Microsystem Improvement Ramp method and formed a collaborative working group. A process map was created to outline the steps and a fishbone analysis was performed to identify barriers and to utilize resources for implementing new interventions. Prior to these interventions, 21 percent of eligible patients had completed annual screening and after the intervention, it rose to 72 percent. The initial completion rate with the first prescription was only 50 percent, but it improved steadily to 54/75 (72 percent) in response to reminder letters sent six weeks after the initial script was given. Close tracking and reminder letters can improve adherence with annual OGTT screening for CFRD among CF patients, with special emphasis on high-risk patients. There should be a special emphasis on screening for CFRD in high-risk CF patients (those with low BMI or higher age). This QI initiative brought about several operational changes in the annual OGTT screening process that have now become the standard operating procedure at the center.

Intrathoracic masses may be detected asymptomatically or cause symptoms due to the compression of... more Intrathoracic masses may be detected asymptomatically or cause symptoms due to the compression of surrounding normal tissues or organs. Mediastinal masses may be encountered at practically any age and may result from a myriad of causes, and are sometimes detected in otherwise asymptomatic patients. Mediastinal masses are less frequently detected in pediatric patients compared with adult patients, and the spectrum of mediastinal masses in children differs from those encountered in adults. The approach to a mediastinal mass requires careful assessment of the location, appearance, and relationship of the mass to the surrounding structures. The differential diagnostic considerations for mediastinal masses can be broad, but careful assessment coupled with additional directed testing can often narrow the differential considerations. We report the case of a 14-year-old boy with an incidentally detected mediastinal mass at chest radiography that, on further evaluation , led to a very unusual diagnosis. This report highlights the differential diagnoses that were considered for this mediastinal mass and the diagnostic evaluation that led to the final diagnosis.

Background: Vocal cord dysfunction (VCD) or paradoxical vocal-fold motion (PVFM) is a functional ... more Background: Vocal cord dysfunction (VCD) or paradoxical vocal-fold motion (PVFM) is a functional disorder of the vocal cords that requires multidisciplinary treatment. Besides relaxation techniques, the use of psychological interventions can help treat the underlying psychological co-morbidities. There is currently no literature that examines the
effectiveness of psychological interventions for VCD/PVFM.
Objectives:To review the evidence for psychological interventions used for the treatment of patients with VCD/PVFM.
Data sources: We searched electronic databases for English medical literature using Pubmed (Medline), PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Registry of ControlledTrials, and Clinicaltrials.gov.The date range for our search is from June 1964 to June 2014.
Study eligibility criteria, participants, and interventions: We included studies that reported the use of psychological interventions in both adults and children diagnosed with VCD/PVFM.We included randomized controlled trials, case-control studies, retrospective chart reviews, prospective case series, and individual case reports.
Results: Most reported studies are small case series or individual case reports that have described the use of interventions such as psychotherapy, behavioral therapy, use of anti anxiety and anti-depressant medications, and hypnotherapy in conjunction with breathing
exercises taught by speech therapists for symptomatic relief. Among the various psychological interventions that have been reported, there is no data regarding effectiveness and/or superiority of one approach over another in either adult or pediatric patients.
Conclusions: Psychological interventions have a role to play in the management of adult and pediatric patients with VCD/PVFM. Future prospective studies using uniform approaches for treatment of associated psychopathology may help address this question.

Purpose: Measurement of socioeconomic status (SES) is traditionally based on education, income, a... more Purpose: Measurement of socioeconomic status (SES) is traditionally based on education, income, and occupation. This information may not be readily available from adolescents participating in research. Methods: Using data from school-based randomized trial of an asthma intervention targeting urban adolescents, we compared percent poverty in zip code of residence (% poverty), median housing value, and parental income and education, to teen responses on the Home Affluence Scale for Children (HASC), which included home, car, and computer ownership for the family and eligibility for free school lunch. The association of HASC with measures of asthma control was also assessed. Results: Of 422 adolescents, 390 (92%) responded to HASC items (mean HASC ¼ 2.5). HASC was associated with mother's education and household income (both P < .001), and significantly correlated with % poverty (P < .0001) and median home value (P ¼ .003). The association of HASC <2.0 to indicators of uncontrolled asthma was in the direction hypothesized, especially for nighttime symptoms, odds ratio (95% confidence interval) ¼ 1.59 (0.95e2.66) and restricted activity, odds ratio ¼ 1.87 (1.12e3.12). Conclusions: HASC correlates well with more traditional measures of SES, and the risk estimates for HASC less than 2.0 and indicators of uncontrolled asthma were mostly in the hypothesized direction. Methods of obtaining SES indicators from youth are needed for research studies.

Annals of Allergy, Asthma & Immunology, Oct 1, 2012

The Journal of …, Jan 1, 2011

Current Opinion in HIV and AIDS, Jan 1, 2010

Dengue Bulletin, Jan 1, 2005

Pediatric Pulmonology, 2015

International Journal of Health Care Quality Assurance, 2015

Annals of Allergy, Asthma & Immunology, Oct 1, 2012

IL-23 is required for effective IL-17 responses to aerosol infection with Mycobacterium tuberculo... more IL-23 is required for effective IL-17 responses to aerosol infection with Mycobacterium tuberculosis (Mtb), however it does not appear to impact early control of bacterial growth in the lung. By extending the time course of infection using mice deficient for the p19 component of the IL-23 cytokine, we report that there is increased bacterial growth in the lungs of these mice compared to wild type infected mice. This increased bacterial growth is associated with decreased maintenance of B cell follicles within lungs of infected mice. While mRNA expression for molecules associated with limiting bacterial growth such as Interferon gamma (IFN) were equivalent between wild type and IL-23p19 deficient mice, reduced expression of both IL-17 and IL-22 mRNA was observed in IL-23p19 deficient Mtb-infected lungs. Importantly, we show that in mice deficient for IL-23p19, B cell follicle size was reduced during chronic Mtb infection and this was temporally associated with the increased bacterial burden. In mice deficient in the IL-17 receptor (IL-17R), B cell follicle generation was affected early in infection whereas the absence of IL-22 influenced the size of B cell follicles in the mid-term. Interestingly, the absence of IL-22 or IL-17R alone did not impact bacterial control. Thus, we show novel data that while IL-23 is required for long term control of Mtb growth in the lung, there is a compensatory effect of IL-22 and IL-17 during tuberculosis.

Interferon-gamma (IFN) is essential for limiting Mycobacterium tuberculosis infection. Using the ... more Interferon-gamma (IFN) is essential for limiting Mycobacterium tuberculosis infection. Using the mouse model, we have recently shown that vaccination triggered accelerated Interleukin-17 (IL-17) and IFN responses by CD4+ T cells in the lung during M. tuberculosis aerosol challenge. We propose that vaccination induces IL-17- producing CD4+ T cells that populate the lung and, after challenge, trigger the production of chemokines. The induction of chemokines results in recruitment of IFN-producing CD4+ T cells from the lymphoid compartment and ultimately restricts bacterial growth. The differential ability of IL-17-producing memory cells to populate the lung compared to the IFN--producing cells suggests that these two cell types differ in their ability to migrate in response to chemokines. In support of this, our data using adoptive transfer models and chemotaxis assays suggests that differential responsiveness to chemokines and retention in different organs may provide the basis for the differential tissue distribution of these two cell types. During progression from effector to memory T cells, we also show differential expression of activation markers on IL17-producing and IFN-producing T cells. This information will lead us to determine whether altering the nature of the lung-resident IL-17 producing population impacts protective efficacy of the recall response to M.tuberculosis challenge.

This work was supported by AI075106 -01 and Children's Hospital of Pittsburgh.

Rationale: The pathogenesis of RSV infection is related to both viral replication and poorly regu... more Rationale: The pathogenesis of RSV infection is related to both viral replication and poorly regulated inflammatory responses.
Lipoxins (LX) are arachidonic acid (AA) derivatives responsible for active termination of inflammation. Elastase is an enzyme
produced by neutrophils and macrophages that assists in nonspecific destruction of infected cells. The role of LX and elastase in
the pathogenesis of RSV bronchiolitis has not been investigated.
Methods: Nasopharyngeal secretions (NPS) obtained from infants with RSV bronchiolitis at admission were tested by ELISA for
various AA metabolites, including the novel class of Lipoxins, as well as neutrophil elastase activity, and were analyzed for their
relationship to illness severity.
Results: Of 25 patients (mean age 10.2 months) hospitalized with RSV bronchiolitis, 5 required ICU admission, and one required
mechanical ventilation. Mean duration of O2 supplementation was 46.3 hours, and average length of stay was 4.8 days.
Elastase activity in NPS was associated with improved oxygenation (p = 0.038) and reduced duration of O2 need (p = 0.015).
Conversely, increased LXA4 in NPS were associated with greater hypoxia (p = 0.047), higher respiratory rate (p = 0.036), and
more prolonged O2 need (p = 0.017), with same being true for LXA4/elastase ratio.
Conclusions: In the absence of adaptive cytotoxic responses, eradication of RSV infection depends on innate immune responses
such as elastase. The emergence of anti−inflammatory mechanisms (LXA4) before virus has been eradicated adversely affects
the outcome of RSV infection. These findings suggest new therapeutic approaches to RSV infection.

"Background: Topiramate and zonisamide are used as anticonvulsant medications in children, and T... more "Background: Topiramate and zonisamide are used as anticonvulsant
medications in children, and Topiramate is also used for migraine prophylaxis. There are reports of topiramate and zonisamide causing oligohydrosis as a side-effect (Clin Neuropharmacol 2008; 31: 339-346, Pediatr Neurol 2003; 28: 184-189), but their effect on sweat chloride levels has not been studied systematically (Indian Pediatr 2008; 45: 238-240).
Hypothesis: Topiramate and zonisamide not only reduce sweat production, but they can also cause elevation of sweat electrolytes.
Methods: Eighteen patients who were receiving topiramate or zonisamide therapy for at least 6 months were enrolled either from Neurology outpatient clinic or Epilepsy Monitoring Unit, and were only included in the study if they had no signs or symptoms and a negative family history of cystic fibrosis. Patients underwent pilocarpine iontopheresis and sweat collection via Macroduct system (Wescor Inc., Logan, UT) as per Clinical and Laboratory Standards Institute (CLSI) and Cystic Fibrosis Foundation (CFF) guidelines. The samples were analyzed the same day using a chloridometer and the mean sweat chloride values were compared to published normative data (J Pediatr 2008; 153: 758-63) by Student’s t-test.
Results: Of the 18 pts (age range 3-22 years, mean age 9.94 years, sex ratio M:F = 0.44) that were enrolled for this study, 14 adequate samples (>15 µL volume) could be obtained from left arm, and 13 from right arm. There were 14 patients on topiramate and 4 were receiving zonisamide. The mean sweat chloride level was 41.77 ± 18.71 mEq/L from the left arm and 46.475 ± 19.29 mEq/L from the right arm for patients receiving topiramate.
For patients on Zonisamide therapy, the mean sweat chloride level was 29.83 ± 10.00 mEq/L from the left arm, and 36.5 ± 3.54 mEq/L from the right arm. Sweat chloride values and volumes did not correlate with dose of either anticonvulsant (p=0.5).
Overall 7/14 (50%) patients on topiramate or zonisamide had either a borderline (> 40 mEq/L but < 60 mEq/L) or elevated (> 60 mEq/L) sweat chloride test result. Comparing these results to the standard reference values for sweat chloride in the normal population, the mean sweat chloride level of patients on topiramate was noted to be significantly higher (p<0.001) for both arms. There was no significant difference in the mean values for sweat chloride between the topiramate and zonisamide groups for both sides (p>0.05).
The insufficient sweat collection rate was 3/18 (17%) for both arms, and another 3/18 had insufficient sweat collected from one of the arms. This rate is much higher than the goal of <5% inadequate sweat collection rate that is established by CFF for accredited sweat testing laboratories, and suggests that drug-induced oligohydrosis is operative in this patient population.
Conclusions: Topiramate and zonisamide can not only cause oligohydrosis, but they can also elevate sweat chloride levels in patients with no clinical features of cystic fibrosis. Further studies to explore whether this is due to interaction with CFTR or via a different mechanism, are underway."

Am. J. Respir. Crit. Care Med. 2012; 185: A2207.

Introduction: Asthma self-regulation interventions help to improve awareness about asthma care an... more Introduction: Asthma self-regulation interventions help to improve awareness about asthma care and help reinforce positive behavioral
patterns. Management of asthma should not only target symptom control, but also bring about an improvement in Quality of Life (QOL).
Depression is an important co-morbidity in urban teens with asthma but its impact on the effectiveness of educational interventions is not
known.
Methods: The web-based, Puff City asthma management program was developed using tailoring to provide individualized education
related to asthma self-regulation and management, and also to impact negative behaviors that could affect asthma related outcomes. This
program was evaluated with a randomized controlled trial conducted in teenagers from grades 9-11 of six Detroit public high schools. The
intervention group received 4 sessions of web-based tailored messages, while the control group was given generic web-based asthma
education. Assessment of asthma symptoms, depression, and QOL measurements were done through online baseline questionnaires for
teens and a telephone baseline survey for caregivers. Outcomes such as functional status and QOL were assessed based on follow up at 12
months.
Results: Of the 422 teens enrolled, 355 had complete teen and caregiver data for analysis (170 treatment and 185 controls). Prevalence of
depression by randomization assignment was similar for teens (treatment vs. control = 29.4 vs. 24.9%, respectively, p=0.34) and caregivers
(12.4 vs. 13.5%, p=0.75). Analysis was stratified by teen depression at baseline, adjusting for potential confounders using logistic
regression. Depression did not seem to influence intervention effectiveness for functional status, i.e., most adjusted Odds Ratios indicated
intervention benefit regardless of depression status. However, for QOL, intervention benefit seemed to differ by depression status. Among
teens who were depressed, treatment vs. control QOL scores overall, and specifically for the domains related to activities, symptoms, and
emotional functioning respectively, were 4.5 vs. 4.1 (p=0.09), 3.8 vs. 3.7 (p=0.95), 4.7 vs. 4.1 (p=0.078), and 4.9 vs. 4.4 (p=0.010), indicating
intervention benefit for QOL among depressed students. No difference by treatment assignment was noted in QOL for teens without
report of depressive symptoms at baseline.
Conclusions: Results suggest that effect of an asthma self-regulation intervention on QOL can differ by depression
status, in that the intervention effect was greater in teens who met study criteria for depression at baseline compared to
those that did not. Further assessment of self-management educational interventions for asthma should look at how
co-morbidities may alter the intervention effect.

Recent Advances in Pediatrics Neonatal …, Jan 1, 2003

Hypotension and shock in the newborn infants is the usual end-result of a variety of insults in t... more Hypotension and shock in the newborn infants is the usual end-result of a variety of insults in the antepartum, intrapartum and postpartum period. 1 Despite advances in neonatal care, circulatory shock causes serious morbidity and mortality in view of the concomitant complex mechanisms of from fetal-neonatal transition and other unique aspects of neonatal physiology. Premature infants have additional strains during this transition period in the form of immature mechanisms of thermogenesis, reduced glycogen stores and muscle mass for ...

Page 1. Epidemiology, Risk Factors, and Natural History of Chronic Hepatitis C Nalini K. Sharma, ... more Page 1. Epidemiology, Risk Factors, and Natural History of Chronic Hepatitis C Nalini K. Sharma, MD and Averell H. Sherker, MD FRCP (C) ...

The concept of resuscitation arose from the age-old quest of man for bringing the seemingly&a... more The concept of resuscitation arose from the age-old quest of man for bringing the seemingly&#x27;dead&#x27;back to life. We have certainly come a long way from the first reported neonatal resuscitation in the Bible, that describes a Hebrew midwife Puah in Exodus 1: 15-17 who&quot; breathed into the baby&#x27;s mouth to cause the baby to cry...&quot;, to the present day state-of-the-art resuscitation of the newborn; the journey being tough and arduous. 1 The evolution of this whole concept took quite a while but the progress has been slow and ...

Textbook of Pediatric Nutrition, 2006

Advances in Pediatrics, 2007

Rational Antibiotic Practice in Pediatrics, 2006

Medical Emergencies in Children, 2006

Essential Pediatric Nursing, 2003

Essential Pediatric Pulmonology, 2010