Cleveland, OH, United States
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Alkhouri N.,Cleveland Clinic | Fiocchi C.,Digestive Disease Institute | Fiocchi C.,Cleveland Clinic Lerner Research Institute | Dweik R.,Respiratory Institute | And 2 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2015

Background There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease. Aim Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD. Methods A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed. Results Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10-7) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1β showed an inverse relation with clinical disease activity. Conclusions Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD. © 2014 John Wiley & Sons Ltd.


Puwanant S.,Chulalongkorn University | Farha S.,Respiratory Institute | George D.,Respiratory Institute | Sharp J.,Respiratory Institute | And 2 more authors.
Circulation | Year: 2010

Background: We tested the hypothesis that right ventricular (RV) pressure overload affects RV function and further influences left ventricular (LV) geometry, which adversely affects LV twist mechanics and segmental function. Methods and Results: Echocardiographic images were prospectively acquired in 44 patients (age, 46±12 years; 82% women) with evidence of pulmonary hypertension (estimated pulmonary artery systolic pressure, 71±23 mm Hg) and in 44 age-and gender-matched healthy subjects. Patients with intrinsic LV diseases were excluded. RV lateral wall longitudinal strain (LS) and interventricular septal (IVS) LS were reduced in the pulmonary hypertension group compared with control subjects (-15.9±7.6% versus-25.5±6.1%, P<0.001; and-17.3±4.4% versus-20.2±3.9%, P=0.002, respectively), whereas LV lateral wall LS was preserved. RV lateral wall LS and IVS LS, but not LV lateral wall LS, correlated with pulmonary artery systolic pressure (r=0.56, P<0.01; r=0.32, P<0.01) and LV eccentricity index (r=0.57, P<0.01; r=0.57, P<0.01). IVS and LV lateral wall circumferential strain (CS) were both reduced in the pulmonary hypertension group. Although IVS CS and LV lateral wall CS correlated with pulmonary artery systolic pressure and LV eccentricity index, after adjustment of CS for LV eccentricity index, differences between groups persisted for IVS CS (P<0.01) but not LV lateral wall CS (P=0.09). LV torsion was decreased in patients with pulmonary hypertension compared with control subjects (9.6±4.9° versus 14.7±4.9°, P<0.001). LV torsion inversely correlated with pulmonary artery systolic pressure (r=-0.39, P<0.01) and LV eccentricity index (r=-0.3, P<0.01). LV untwisting rates were similar in both groups (P=0.7). Conclusions: Chronic RV pressure overload directly affects RV longitudinal systolic deformation. RV pressure overload further influences IVS and LV geometry, which impairs LV torsion and segmental LS and CS, more for the IVS than for the free wall of the LV. © 2010 American Heart Association. All rights reserved.


Gendelman S.,Respiratory Institute | Zeft A.,Orthopedic and Rheumatologic Institute | Zeft A.,Cleveland Clinic | Spalding S.J.,Orthopedic and Rheumatologic Institute | Spalding S.J.,Cleveland Clinic
Journal of Rheumatology | Year: 2013

Objective. To date only 38 cases of childhood-onset eosinophilic granulomatosis with polyangiitis (cEGPA; formerly Churg-Strauss syndrome) have been reported. Additional patients with cEGPA could enhance the understanding of this rare and life-threatening condition. Our objectives were (1) to determine the frequency of specific organ system involvement; (2) to examine initial therapeutic regimen; and (3) to document disease and therapy-related morbidity in a contemporary cohort of patients with cEGPA. Methods. Retrospective review of patients evaluated at the Cleveland Clinic between 2003 and 2011 who met either American College of Rheumatology or Lanham criteria for EGPA and whose age was < 18 years at symptom onset. Results. Nine patients (8 female; 7 white) were identified. Median age at onset of rhinitis/asthma symptom was 13 years and median age at diagnosis of cEGPA was 15 years. All patients demonstrated eosinophilia, upper airway disease (allergic rhinitis, chronic sinusitis, and/or nasal polyps), and pulmonary involvement. Other frequently involved organ systems included musculoskeletal (67%), gastrointestinal (67%), cutaneous (67%), neurologic (56%), and cardiac (44%). Antineutrophil cytoplasmic antibody (ANCA) serologies were negative in all patients. The medications used most frequently for initial therapy included oral (44%) or intravenous corticosteroids (56%) and azathioprine (67%). Disease or therapeutic complications occurred in half of the cohort and included heart failure, stroke, and sequela from longterm, high-dose steroids. Conclusion. Eosinophilia, in combination with upper airway, pulmonary, musculoskeletal, neurologic, and cardiac manifestations, is frequently observed in cEGPA. ANCA titers are often negative. Steroids are the mainstay of initial therapy but steroid-related side effects occur regularly. Copyright © 2013. All rights reserved.


Choi H.,Respiratory Institute | Choi H.,Case Western Reserve University | Mazzone P.,Respiratory Institute
Cleveland Clinic Journal of Medicine | Year: 2014

Radon is a naturally occurring radioactive gas. Its progenies emit alpha particles capable of causing tissue damage. Radon exposure is estimated to be the second most common cause of lung cancer in the United States. Management of patients with a history of radon exposure should involve a lung cancer specialist.


Kaw R.,Cleveland Clinic | Bhateja P.,Respiratory Institute | Mar H.P.,Medicine Institute Center for Value Based Care Research | Hernandez A.V.,Cleveland Clinic Lerner Research Institute | And 3 more authors.
Chest | Year: 2016

BACKGROUND: Among patients with OSA, a higher number of medical morbidities are known to be associated with those who have obesity hypoventilation syndrome (OHS) compared with OSA alone. OHS can pose a higher risk of postoperative complications after elective noncardiac surgery (NCS) and often is unrecognized at the time of surgery. The objective of this study was to retrospectively identify patients with OHS and compare their postoperative outcomes with those of patients with OSA alone. METHODS: Patients meeting criteria for OHS were identified within a large cohort with OSA who underwent elective NCS at a major tertiary care center. We identified postoperative outcomes associated with OSA and OHS as well as the clinical determinants of OHS (BMI, apnea-hypopnea index [AHI]). Multivariable logistic and linear regression models were used for dichotomous and continuous outcomes, respectively. RESULTS: Patients with hypercapnia from definite or possible OHS and overlap syndrome are more likely to experience postoperative respiratory failure (OR, 10.9; 95% CI, 3.7-32.3; P .0001), postoperative heart failure (OR, 5.4; 95% CI, 1.9-15.7; P = .002), prolonged intubation (OR, 3.1; 95% CI, 0.6-15.3; P = .2), postoperative ICU transfer (OR, 10.9; 95% CI, 3.7-32.3; P .0001), and longer ICU (b-coefficient, 0.86; SE, 0.32; P = .009) and hospital (b-coefficient, 2.94; SE, 0.87; P = .0008) lengths of stay compared with patients with OSA. Among the clinical determinants of OHS, neither BMI nor AHI showed associations with any postoperative outcomes in univariable or multivariable regression. CONCLUSIONS: Better emphasis is needed on preoperative recognition of hypercapnia among patients with OSA or overlap syndrome undergoing elective NCS. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.


Bukstein D.,Respiratory Institute | Luskin A.T.,Respiratory Institute | Farrar J.R.,Life science Press
Allergy and Asthma Proceedings | Year: 2011

Medical advances have allowed many patients with chronic diseases to lead relatively normal lives, but disparity between patient perceptions of "normal" and therapeutically defined disease control contributes to lowered adherence to treatment. This disconnect is greatest in diseases such as allergic rhinitis (AR) in which patients experience varying symptom severity over time - from asymptomatic periods to episodes of severe illness. This study was designed to evaluate the concept of adherence as applied to patients with AR. We reviewed the published literature. Adherence (or nonadherence) is an active process involving decision making on the part of the patient. Poor adherence with therapy can be the major barrier to achieving disease control, and the "on again, off again" approach to AR treatment embraced purposely by some patients may contribute to symptom lability, disease exacerbations, and higher costs. Evidence from surveys suggests that although specific educational interventions can temporarily improve adherence, in the long term most patients eventually revert to their former behavior. The available data suggest a need to reappraise how we address adherence with therapy in patients with chronic diseases with variable symptoms such as AR. The question is not just whether patient behavior can conform to recommended treatment plans, but whether it should. Experience suggests that successful strategies will be brief, easy to use, and capable of being tailored to individual patients in diverse clinical settings. Increased flexibility with medications is a corollary, particularly when patients are relatively asymptomatic (i.e., considered in control). Copyright © 2011, OceanSide Publications, Inc.


Tonelli A.R.,Respiratory Institute | Zein J.,Respiratory Institute | Ioannidis J.P.A.,Stanford University
Cardiovascular Therapeutics | Year: 2013

Objective: We studied the entire agenda of randomized clinical trials in pulmonary hypertension (PH) using sociological methods. We explored the geometry of the PH network to interpret the evidence on multiple competing treatments for the same indication. Design: We searched MEDLINE, Embase and Cochrane Library Databases for published studies. We queried clinicaltrials.gov and WHO International Clinical Trials Registry platform for non-published studies. Results: We found 75 randomized trials (41 published [n = 4136 participants] and 34 registered unpublished [planned n = 3470 participants]). Of the published randomized studies, all used placebo as the comparator arm except for two nonindustry-sponsored comparisons between phosphodiestearase-5 (PDE-5) inhibitors and endothelin receptor antagonists (ERA), and one study comparing two different regimens of treprostinil. Similarly, only five unpublished/ongoing trials used an active PH treatment as comparator (PDE-5 inhibitors versus ERA (n = 3), different doses of sildenafil (n = 1) and two formulations of epoprostenol (n = 1). Of the 75 trials, 47 were sponsored by the manufacturer of the tested active product(s), and only two trials were sponsored by two companies comparing their products. Conclusions: The relative merits of different treatment options are not directly known, as there are very few head-to-head comparisons. A limited number of ongoing studies are using active FDA-approved PH-treatments for comparison. This lack of information can be overcome by carefully designing comparative effectiveness trials. © 2013 John Wiley & Sons Ltd.


Mohanka M.,Respiratory Institute | Khemasuwan D.,Respiratory Institute | Stoller J.K.,Respiratory Institute
Expert Opinion on Biological Therapy | Year: 2012

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a relatively common, but under-recognized condition which manifests commonly with liver cirrhosis and emphysema. Specific therapy for lung-affected individuals with AATD is augmentation therapy, which consists of intravenous infusion of purified human plasma-derived alpha-1 antitrypsin (AAT). Augmentation therapy was first approved by the United States Food and Drug Administration (FDA) in 1987 for emphysema associated with severe AATD and today, six augmentation therapy preparations, all of which derive from pooled human plasma, have received FDA approval. Areas covered: This paper reviews augmentation therapy for AATD, including the various available commercial preparations, their processing and biochemical differences, evidence regarding biochemical and clinical efficacy, patterns of clinical use, adverse effect profiles, cost-effectiveness and potential uses in conditions other than emphysema associated with AATD. Novel and emerging strategies for treating AATD are briefly discussed next, including alternative dosing and administration strategies, recombinant preparations, small molecule inhibitors of neutrophil elastase and of AAT polymerization, autophagy-enhancing drugs and gene therapy approaches. Expert opinion: We conclude with a discussion of our approach to managing patients with AATD and use of augmentation therapy. © 2012 Informa UK, Ltd.


Tonelli A.R.,Respiratory Institute
Current Opinion in Pulmonary Medicine | Year: 2013

PURPOSE OF REVIEW: This review discusses the current impact of pulmonary hypertension on the outcome and treatment of cystic fibrosis (CF). RECENT FINDINGS: Pulmonary hypertension is commonly encountered in advanced lung diseases such as CF. The prevalence of pulmonary hypertension in CF patients varies based on disease severity and methodology used for diagnosis. Chronic alveolar hypoxia is the most likely cause. The majority of recent studies have shown worse survival in CF patients who develop pulmonary hypertension. The impact of pulmonary hypertension-specific therapies on symptomatology and outcomes in CF patients has not been well studied. SUMMARY: Pulmonary hypertension is common in patients with CF and it occurs largely because of hypoxemia. The presence of pulmonary hypertension in patients with CF is likely associated with worse outcome; however, it remains unknown whether treatment with pulmonary hypertension-specific therapies would be beneficial. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Tonelli A.R.,Respiratory Institute | Zein J.,Respiratory Institute | Adams J.,Respiratory Institute | Ioannidis J.P.A.,Stanford University
Intensive Care Medicine | Year: 2014

Purpose: Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses. Methods: We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring. Results: We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)-44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 metaanalyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS. Conclusions: There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses. © 2014 Springer-Verlag Berlin Heidelberg and ESICM.

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