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Cleveland, OH, United States

Kurada S.,Medicine Institute | Alkhouri N.,Cleveland Clinic | Fiocchi C.,Digestive Disease Institute | Fiocchi C.,Cleveland Clinic Lerner Research Institute | And 3 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.


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.


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.


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.


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.

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