Obstructive Physiology Research Articles

SMALL CELL CARCINOMA PRESENTING AS A MASSIVE BIATRIAL MASS WITH OBSTRUCTIVE PHYSIOLOGY DIAGNOSED BY UPPER ENDOSCOPIC ULTRASOUND GUIDED FINE NEEDLE ASPIRATION

We present a rare case of small cell carcinoma presenting as a massive biatrial mass with obstructive physiology at a high risk of hemodynamic collapse. A 31 year-old male presented with 6 weeks of shortness of breath. He was found to have a 15 centimeter neoplasm occupying both atria, obliterating

Risk modifiers of acute respiratory distress syndrome in patients with non-pulmonary sepsis: a retrospective analysis of the FORECAST study

BackgroundPredisposing conditions and risk modifiers instead of causes and risk factors have recently been used as alternatives to identify patients at a risk of acute respiratory distress syndrome (ARDS). However, data regarding risk modifiers among patients with non-pulmonary sepsis is rare.MethodsWe conducted a secondary analysis of the multicenter, prospective, Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) cohort study that was conducted in 59 intensive care units (ICUs) in Japan during January 2016–March 2017. Adult patients with severe sepsis caused by non-pulmonary infection were included, and the primary outcome was having ARDS, defined as meeting the Berlin definition on the first or fourth day of screening. Multivariate logistic regression modeling was used to identify risk modifiers associated with ARDS, and odds ratios (ORs) and their 95% confidence intervals were reported. The following explanatory variables were then assessed: age, sex, admission source, body mass index, smoking status, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, steroid use, statin use, infection site, septic shock, and acute physiology and chronic health evaluation (APACHE) II score.ResultsAfter applying inclusion and exclusion criteria, 594 patients with non-pulmonary sepsis were enrolled, among whom 85 (14.3%) had ARDS. Septic shock was diagnosed in 80% of patients with ARDS and 66% of those without ARDS (p = 0.01). APACHE II scores were higher in patients with ARDS [26 (22–33)] than in those without ARDS [21 (16–28), p < 0.01]. In the multivariate logistic regression model, the following were independently associated with ARDS: ICU admission source [OR, 1.89 (1.06–3.40) for emergency department compared with hospital wards], smoking status [OR, 0.18 (0.06–0.59) for current smoking compared with never smoked], infection site [OR, 2.39 (1.04–5.40) for soft tissue infection compared with abdominal infection], and APACHE II score [OR, 1.08 (1.05–1.12) for higher compared with lower score].ConclusionsSoft tissue infection, ICU admission from an emergency department, and a higher APACHE II score appear to be the risk modifiers of ARDS in patients with non-pulmonary sepsis.

Association of Obesity With Adverse Long-term Outcomes in Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy (HCM) are prone to body weight increase and obesity. Whether this predisposes these individuals to long-term adverse outcomes is still unresolved. To describe the association of body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) with long-term outcomes in patients with HCM in terms of overall disease progression, heart failure symptoms, and arrhythmias. In this cohort study, retrospective data were analyzed from the ongoing prospective Sarcomeric Human Cardiomyopathy Registry, an international database created by 8 high-volume HCM centers that includes more than 6000 patients who have been observed longitudinally for decades. Records from database inception up to the first quarter of 2018 were analyzed. Patients were divided into 3 groups according to BMI class (normal weight group, <25; preobesity group, 25-30; and obesity group, >30). Patients with 1 or more follow-up visits were included in the analysis. Data were analyzed from April to October 2018. Association of baseline BMI with outcome was assessed. Outcome was measured against overall and cardiovascular mortality, a heart failure outcome (ejection fraction less than 35%, New York Heart Association class III/IV symptoms, cardiac transplant, or assist device implantation), a ventricular arrhythmic outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator therapy), and an overall composite outcome (first occurrence of any component of the ventricular arrhythmic or heart failure composite end point, all-cause mortality, atrial fibrillation, or stroke). Of the 3282 included patients, 2019 (61.5%) were male, and the mean (SD) age at diagnosis was 47 (15) years. These patients were observed for a median (interquartile range) of 6.8 (3.3-13.3) years. There were 962 patients in the normal weight group (29.3%), 1280 patients in the preobesity group (39.0%), and 1040 patients in the obesity group (31.7%). Patients with obesity were more symptomatic (New York Heart Association class of III/IV: normal weight, 87 [9.0%]; preobesity, 138 [10.8%]; obesity, 215 [20.7%]; P < .001) and more often had obstructive physiology (normal weight, 201 [20.9%]; preobesity, 327 [25.5%]; obesity, 337 [32.4%]; P < .001). At follow-up, obesity was independently associated with the HCM-related overall composite outcome (preobesity vs normal weight: hazard ratio [HR], 1.102; 95% CI, 0.920-1.322; P = .29; obesity vs normal weight: HR, 1.634; 95% CI, 1.332-1.919; P < .001) and the heart failure composite outcome (preobesity vs normal weight: HR, 1.192; 95% CI, 0.930-1.1530; P = .20; obesity vs normal weight: HR, 1.885; 95% CI, 1.485-2.393; P < .001) irrespective of age, sex, left atrium diameter, obstruction, and genetic status. Obesity increased the likelihood of atrial fibrillation but not of life-threatening ventricular arrhythmias. Obesity is highly prevalent among patients with HCM and is associated with increased likelihood of obstructive physiology and adverse outcomes. Strategies aimed at preventing obesity and weight increase may play an important role in management and prevention of disease-related complications.

Usefulness of different prognostic scores for AECOPD: APACHE II, BAP65, 2008, and CAPS scores

PurposeThe purpose of this study was to compare four different scores [Acute Physiology and Chronic Health Evaluation (APACHE II); elevated blood urea nitrogen, altered mental status, pulse >109/min, age >65 years (BAP65); chronic obstructive pulmonary disease (COPD) and Asthma Physiology Score (CAPS); and 2008 score) to test their predictive properties for the need of mechanical ventilation (MV) and short-term mortality in patients with acute exacerbation COPD (AECOPD).Patients and methodsThis study enrolled 100 consecutive patients with acute exacerbation COPD, over a 6-month duration, admitted to the Emergency Department in Alexandria Main University Hospitals. The four scores were calculated for each patient, and clinical data and outcome (need for MV and mortality during hospitalization or within a week after discharge) were recorded.ResultsTheir mean age was 61.1±10.7 years, and 88% were males. Duration of hospital stay was less than or equal to 20 days in 67%. Mortality rate was 4%. Overall, 40% required MV. Blood urea nitrogen, pulse, CO2, pH, altered consciousness, and white blood cell were significant predictors of mortality in univariate but not multivariate analysis. Previous MV, cyanosis, and paradoxical abdominal movement were significant predictors of need for MV. The highest area under the receiver operating characteristic curve was that of APACHE II score regarding either mortality prediction [area under the curve (AUC), 0.982; P=0.001] or need for MV (AUC, 0.959; P<0.001), followed by BAP65 score for mortality prediction (AUC, 0.967; P=0.002) and 2008 score for predicting the need for MV (AUC, 0.851; P<0.001).ConclusionAll studied scores correlated significantly with mortality, but only APACHE II and 2008 score correlated significantly with the need for MV. The highest area under the receiver operating characteristic curve was that of APACHE II score regarding either mortality or need for MV prediction. Previous need for MV was the most important predictor for the need for MV. The routine use of these practical scores in triage of patients may direct early interventions to reduce mortality rate.

Survival Differences in Women and Men After Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy

Recent data indicate that women with hypertrophic cardiomyopathy (HCM) are older and more symptomatic at presentation and have worse clinical outcomes than men. However, to our knowledge, there are no large studies of the association of patient sex with outcomes after surgical myectomy. To analyze preoperative characteristics and overall survival of women and men undergoing septal myectomy for obstructive HCM. This retrospective, single-center study included the clinical data of adult patients who underwent septal myectomy from January 1961 through April 2016. Data analysis occurred from December 2017 to December 2018. Septal myectomy. Survival. A total of 2506 adults were included; 1379 patients (55.0%) were men. At the time of surgery, women were older, with median (IQR) age of 59.5 (46.6-68.2) years vs 52.9 (42.9-62.7) years in men (P < .001). Women were more likely to have New York Heart Association class III or IV status at presentation (women, 1023 [90.8%]; men, 1169 [84.8%]; P < .001) and more severe obstructive physiology, as reflected in higher resting left ventricular outflow tract gradients (women, 67.0 [36.0-97.0] mm Hg; men, 50.0 [23.0-81.0] mm Hg; P < .001). Women also had a greater likelihood of having moderate or severe mitral regurgitation (606 [55.2%]) than men (581 [43.1%]; P < .001) and higher right ventricular systolic pressure (women, 36.0 [30.0-46.0] mm Hg; men, 33.0 [28.0-39.0] mm Hg; P < .001). The unadjusted overall survival was lower in women, corresponding to a median 3.9-year shorter survival than men (median [IQR] survival time: women, 18.2 [12.1-27.2] years; men, 22.1 [15.1-32.5] years; P < .001). In a multivariable Cox regression analysis, however, the association between sex and mortality was attenuated and not significant after controlling for other baseline variables (hazard ratio, 0.98 [95% CI, 0.76-1.26]; P = .86). Among the covariates in the model, older age at surgery (adjusted hazard ratio [aHR], 3.09 [95% CI, 2.12-4.52]; P < .001), higher body mass index (aHR, 1.22 [95% CI, 0.90-1.66]; P < .001), greater NYHA class (aHR, 2.31 [95% CI, 1.03-5.15]; P = .04), and presence of diabetes prior to surgery (aHR, 1.57 [95% CI, 1.10-2.24]; P = .01) were each independently associated with increased mortality. Operations performed later in the study period (2013 vs 2004) were associated with decreased mortality (aHR, 0.82 [95% CI, 0.55-1.22]; P = .001). In this large cohort of surgical patients with obstructive HCM, we observed significant differences at clinical presentation between women and men, in that women were older and more symptomatic. However, after adjustment for important baseline prognostic factors, there was no survival difference after septal myectomy by sex. Improved care of women with obstructive HCM should focus on early identification of disease and prompt surgical referral of appropriate patients who do not respond to medical treatment.

New Developments in Esophageal Motility Testing

The purpose of this review is to present the latest developments in esophageal motility testing and summarize the current paradigm of esophageal motility disorders. While high-resolution esophageal pressure topography interpreted according to the Chicago Classification represents the gold standard to evaluate esophageal motility, recent studies highlight the additional value of novel manometric applications. Novel applications include provocative measures to assess for obstructive physiology at the esophagogastric junction (EGJ), esophageal peristaltic reserve, and rumination and supragastric belching disorders. Furthermore, high-resolution impedance manometry provides assessment of bolus flow in relation to pressure changes. Distinct from manometry, the endolumenal functional lumen imaging probe examines esophageal motor response to distension to provide complementary and alternative data with regard to EGJ function and esophageal body motor function. Barium esophagram with timed swallow and barium tablet continues to be an important esophageal motility test. Furthermore, current use of multichannel intraluminal impedance-pH monitoring extends beyond reflux monitoring to measure reflux clearance and esophageal epithelial integrity. The diagnostic armamentarium for esophageal motility disorders has expanded tremendously to include a multitude of sophisticated tools. Advancements in diagnostic technology and understanding of esophageal physiology have shifted the field to more precisely characterize esophageal motility and guide phenotype-driven management.

Abstract 17067: MAVERICK-HCM: Phase 2 Randomized, Multi-Center, Double-Blind, Placebo-Controlled Concentration-Guided Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) carries substantial lifelong morbidity. Mutations in sarcomeric proteins that lead to HCM cause excess contractility, poor relaxation, and inefficient energy utilization. Although obstructive physiology is a prominent feature of disease, approximately 30% of HCM patients experience symptoms in the context of non-obstructive HCM (nHCM). Management options are extremely limited with little other than cardiac transplantation to offer severely affected patients. Mavacamten (MAVA), a first-in-class small molecule, is a selective modulator of cardiac myosin that inhibits the cardiac myosin ATPase to reversibly attenuate cardiac contractility. In addition to its effects on contractility, MAVA has been shown to improve LV compliance in preclinical and clinical studies. The Phase 2 MAVERICK-HCM study is designed to evaluate safety and tolerability, and to provide pilot data on the effects of MAVA on biomarkers, cardiac function, and exercise capacity in nHCM. Methods: This double-blind study will enroll 60 individuals with nHCM (Left ventricular outflow tract gradient &lt;30 mmHg; resting or provoked), NYHA Class II or III, and LVEF ≥55%. Subjects will be randomized 1:1:1 to one of two target plasma drug concentrations (Group 1: ~200 ng/mL and Group 2: ~500 ng/mL) or placebo for 16 weeks. The starting dose of MAVA is 5 mg, with one-step dose titration at Week 6 based on plasma drug concentration. Predefined criteria, including LVEF, will guide study drug discontinuation if indicated. Cardiopulmonary exercise testing will be performed at baseline and Week 16 to assess the impact on exercise capacity. The primary endpoint is the frequency and severity of treatment-emergent adverse events. The study design also includes multiple secondary endpoints including echocardiographic measures of diastolic function, NT-proBNP levels, patient reported outcomes, and physical activity by wearable accelerometer. An independent data monitoring committee will oversee safety. Conclusions: MAVERICK-HCM is testing a novel therapy to improve symptom burden in nHCM; a patient cohort currently lacking effective treatment. By targeting a core molecular mechanism of disease, MAVA has the potential to alter natural history.

TWENTY-FIVE YEAR-OLD MALE ATHLETE WITH COUGH, EXERTIONAL DYSPNEA, AND HISTORY OF PNEUMONIA

Introduction Wheezing and cough in the young adult are common chief concerns most commonly attributable to asthma. In a patient with no history of atopy, other diagnoses should be considered. Case Description A 25-year old African-American male, athlete, nonsmoker with past medical history of sickle cell trait presented to his practitioner with one year of cough, mucus production and exertional dyspnea. The patient had been hospitalized at 17 years-of-age with pneumonia, after which he developed shingles. He was prescribed albuterol and fluticasone-propionate inhalers without relief, so was referred to pulmonology. His lung exam was notable for late expiratory wheezes and rhonchi in the lower lung fields and pulmonary function tests showed mixed restrictive and obstructive physiology. Labs revealed leukopenia and elevated CRP, and CT chest showed bilateral lower lobe bronchiectasis. He was referred to immunology. On evaluation, initial labs revealed elevated total IgG and IgG1, normal C3, low C4, and reduced total complement activity ( Discussion C8 deficiency is a very rare immune deficiency involving the terminal pathway of the complement system, characterized by reduced total complement activity and reduced alternative complement pathway function.1 Typical manifestations include recurrent meningitis and sepsis, most commonly due to Neisseria.2 Administration of meningococcal and pneumococcal vaccines2 and antibiotic prophylaxis3 are documented treatment components. Table 1: Pertinent Laboratory Values

Esophagogastric Junction Outflow Obstruction: Features, Etiology, and Outcome in a Single-Center Experience - Time for Standardization?

Introduction: Esophagogastric junction outflow obstruction (EGJOO) is defined by the Chicago classification as an elevated integrated relaxation pressure of >15 mm of Hg with preserved peristalsis. This esophageal motility disorder is increasingly recognized and while suggesting obstructive physiology, it does not describe a specific diagnosis. Variant/incompletely expressed achalasia, mechanical obstruction and artifact have all been described as causes. Methods: Aim: To describe the clinical characteristics and outcomes in a cohort of patients with EGJOO. Study design: Consecutive adult patients undergoing high resolution manometry (HRM) between 1/2/17 and 12/31/17 with a diagnosis of EGJOO were identified. Records were reviewed to determine: 1. causes of EGJOO 2.treatment and outcome. Results: Of 839 HRM studies performed, 68 (8.1%) met criteria for EGJOO. Mean age of this patient cohort was 57.6 years. 38 (55.9%) had dysphagia, 12 (17.6%) regurgitation, 6 (8%) heartburn and remainder with miscellaneous symptoms (cough, chest pain). 9 patients had prior gastric/esophageal surgery. 41 patients were evaluated with barium esophagram (BS) - of these 68.3% were abnormal. 36 patients were evaluated by upper endoscopy - 61.1 % showed abnormalities including hiatal hernia, esophagitis, or evidence of prior surgery. Esophageal biopsies in 21 patients excluded eosinophilic esophagitis. 11 had surgical interventions (Refer to figure 1). All had clinical improvement on follow up. Conclusion: EGJOO is frequently found (8%) and comprises a heterogeneous group with obstructive physiology presenting most commonly with dysphagia (56%). Benign anatomic abnormalities such as hiatal hernia are the most common associated anatomic findings as detected by BS (68.3%) or endoscopy (63.2%). Surgical treatment of hiatal hernia associated EGJOO does not subsequently result in dysphagia. Treatment of EGJOO as presumed early or variant expression achalasia is uncommon (5.8%); treatment results in improved symptoms. 402 Figure 1. Evaluation and management of a cohort of patients diagnosed with EGJOO in 2017.

Dural venous sinus stenting for idiopathic intracranial hypertension: An updated review

BackgroundDural venous sinus stenting (DVSS) is an accepted treatment option in selected patients with medically refractory idiopathic intracranial hypertension and obstructive venous outflow physiology prior to cerebrospinal flow diversion (CSFD) surgery. There are no randomized controlled studies focusing on outcomes and complication rates for dural venous sinus stenting. PurposeWe present the largest comprehensive meta-analysis on DVSS for idiopathic intracranial hypertension (IIH) focusing on success rates, complications, and re-stenting rates to date. We also present a simplified approach to direct retrograde internal jugular vein (IJ) access for DVSS that allows for expedited procedures. Materials and methodsWe performed a retrospective electronic PubMed query of all peer-reviewed articles in the last 15 years between 2003 to 2018. We included all patients who underwent dural venous sinus stenting for a medically refractive IIH and excluded articles without sufficient data on outcomes, complication rates and re-stenting rates. We also evaluated and compared outcomes in patients undergoing direct retrograde IJ access DVSS to traditional transfemoral vein access. ResultsA total of 29 papers and 410 patients who underwent DVSS met criteria for inclusion. DVSS was associated with high technical success [99.5%], low rates of repeated procedure [10%], and low major complication rates [1.5%]. ConclusionOur retrospective comprehensive review of DVSS for medically refractory IIH suggests that stenting in appropriately chosen patients is associated with low complication rates, high technical success, and low repeat procedure rates.

Respiratory Symptoms in Young Adults and Future Lung Disease. The CARDIA Lung Study.

There are limited data on factors in young adulthood that predict future lung disease. To determine the relationship between respiratory symptoms, loss of lung health, and incident respiratory disease in a population-based study of young adults. We examined prospective data from 2,749 participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study who completed respiratory symptom questionnaires at baseline and 2 years later and repeated spirometry measurements over 30 years. Cough or phlegm, episodes of bronchitis, wheeze, shortness of breath, and chest illnesses at both baseline and Year 2 were the main predictor variables in models assessing decline in FEV1 and FVC from Year 5 to Year 30, incident obstructive and restrictive lung physiology, and visual emphysema on thoracic computed tomography scan. After adjustment for covariates, including body mass index, asthma, and smoking, report of any symptom was associated with -2.71 ml/yr excess decline in FEV1 (P < 0.001) and -2.18 in FVC (P < 0.001) as well as greater odds of incident (prebronchodilator) obstructive (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.14) and restrictive (OR, 1.40; 95% CI, 1.09-1.80) physiology. Cough-related symptoms (OR, 1.56; 95% CI, 1.13-2.16) were associated with greater odds of future emphysema. Persistent respiratory symptoms in young adults are associated with accelerated decline in lung function, incident obstructive and restrictive physiology, and greater odds of future radiographic emphysema.

Interferon response to respiratory syncytial virus by bronchial epithelium from children with asthma is inversely correlated with pulmonary function

Respiratory viral infection in early childhood, including that from respiratory syncytial virus (RSV), has been previously associated with the development of asthma. We aimed to determine whether exvivo RSV infection of bronchial epithelial cells (BECs) from children with asthma would induce specific gene expression patterns and whether such patterns were associated with lung function among BEC donors. Primary BECs from carefully characterized children with asthma (n=18) and matched healthy children without asthma (n=8) were differentiated at an air-liquid interface for 21days. Air-liquid interface cultures were infected with RSV for 96hours and RNA was subsequently isolated from BECs. In each case, we analyzed gene expression using RNA sequencing and assessed differences between conditions by linear modeling of the data. BEC donors completed spirometry to measure lung function. RSV infection of BECs from subjects with asthma, compared with uninfected BECs from subjects with asthma, led to a significant increase in expression of 6199 genes. There was significantly greater expression of 195 genes in BECs from children with asthma and airway obstruction (FEV1/forced vital capacity<0.85 and FEV1<100% predicted) than in BECs from children with asthma without obstruction, or in BECs from healthy children. These specific genes were found to be highly enriched for viral response genes induced in parallel with types I and III interferons. BECs from children with asthma and with obstructive physiology exhibit greater expression of types I and III interferons and interferon-stimulated genes than do cells from children with normal lung function, and expression of interferon-associated genes correlates with the degree of airway obstruction. These findings suggest that an exaggerated interferon response to viral infection by airway epithelial cells may be a mechanism leading to lung function decline in a subset of children with asthma.

Clinical and Biological Insights from the University of California San Francisco Prospective and Longitudinal Cohort

Sarcoidosis is a systemic inflammatory disease characterized by non-necrotizing granulomas in involved organs, most commonly the lung. Description of patient characteristics in the Western United States is limited. Furthermore, blood-based measures that relate to clinical sarcoidosis phenotypes are lacking. We present an analysis of a prospective, longitudinal sarcoidosis cohort at a Northern Californian academic medical center. We enrolled 126 sarcoidosis subjects and 64 healthy controls and recorded baseline demographic and clinical characteristics. We used regression models to identify factors independently associated with pulmonary physiology. We tested whether blood transcript levels at study entry could relate to longitudinal changes in pulmonary physiology. White, non-Hispanics composed ~70% of subjects. Hispanics and Blacks had a diagnostic biopsy at an age ~7years younger than whites. Obstructive, but not restrictive, physiology characterized Scadding Stage IV patients. Subjects reporting use of immunosuppression had worse FEV1%p, FVC%p, and DLCO%p compared to subjects never treated, regardless of Scadding stage. We defined sarcoidosis disease activity by a drop in pulmonary function over 36months and found that subjects meeting this definition had significant repression of blood gene transcripts related to T cell receptor signaling pathways, referred to as the "TCR factor." Obstructive pulmonary physiology defined Stage IV patients which were mostly white, non-Hispanics. Genes comprising the composite gene expression score, TCR factor, may represent a blood-derived measure of T-cell activity and an indirect measure of active sarcoidosis inflammation. Validation of this measure could translate into individualized treatment for sarcoidosis patients.

Evaluation of visual and computer-based CT analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis.

To determine whether computer-based quantification (CALIPER software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP). A total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and CALIPER. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO ) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices. CALIPER-derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (CALIPER R = 0.73, visual R = 0.51); DLCO (CALIPER R = 0.61, visual R = 0.48); and CPI (CALIPER R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was CALIPER pulmonary vessel volume (PVV): FVC R = 0.75, DLCO R = 0.68 and CPI R = 0.76. Ground-glass opacity quantified by CALIPER alone demonstrated strong associations with restrictive functional indices: CALIPER FVC R = 0.65; DLCO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by CALIPER was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (CALIPER R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis. CALIPER improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by CALIPER demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel CALIPER variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new automated index of disease severity in HP.

Bronchodilator effects of ipratropium bromide and albuterol sulfate among subjects with tetraplegia

Objective: In addition to lung volume restriction, persons with chronic tetraplegia demonstrate obstructive airway physiology evinced by pharmacologically-induced bronchodilation. We previously found independent evidence that anticholinergic agents (ipratropium bromide; IB) and beta-2 adrenergic agonists (albuterol sulfate; AS) were associated with significant bronchodilation in subjects with tetraplegia as determined via spirometry or body plethysmography. Direct comparison of these two classes of agents has received little attention.Methods: Twelve subjects with chronic tetraplegia completed single dose treatment on alternate days with nebulized IB or AS. Patients underwent pre- and 30-minute post-bronchodilator spirometry, body plethysmography, and impulse oscillation system (IOS) in accordance with established protocols.Results: Spirometry and specific airway conductance revealed significant bronchodilator responsiveness following both IB and AS. As determined by increases in specific airway conductance post-bronchodilator, IB tended toward greater bronchodilation than AS (71% vs. 47%). IOS revealed a greater reduction in central airway resistance (R20) following IB compared to AS (22% vs. 9%, P < 0.01). A greater number of subjects exhibited a clinically significant reduction in R20 following IB compared to AS (58% vs. 8%, P < 0.01).Conclusion: Among subjects with tetraplegia, both IB and AS elicit significant bronchodilation, although the magnitude of the bronchodilator response is greater following IB. This lends support to theory of overriding cholinergic airway tone in tetraplegia. The IOS findings further suggest that the predominant site of action of IB is upon the larger central airways congruent with findings in able-bodied subjects.

Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: the INHERIT randomised, double-blind, placebo-controlled trial

No medical treatment has been reliably shown to halt or reverse disease progression in hypertrophic cardiomyopathy, but the results of several pilot studies have suggested beneficial effects of angiotensin II receptor blockers on left ventricular hypertrophy and fibrosis, which are predictive of an adverse outcome. We aimed to assess the effect of the angiotensin II receptor blocker losartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. In this single-centre, randomised, double-blind, placebo-controlled trial, adult patients (aged 18 years and older) with obstructive or non-obstructive hypertrophic cardiomyopathy were randomly assigned via computer-based system to losartan (100 mg per day) or placebo for 12 months. Patients and investigators were masked to assigned treatment. The primary endpoint was change in left ventricular mass as assessed by cardiac magnetic resonance imaging (CMR) or CT. Efficacy analyses were done in the modified intention-to-treat population (all patients with data available at the 12-month follow-up). The trial is registered with ClinicalTrials.gov, number NCT01447654. Between Dec 1, 2011, and May 1, 2013, 318 patients were screened. 133 patients (mean age 52 years [SD 13], 35% women) consented and were randomly assigned to placebo (n=69) or losartan (n=64). 124 (93%) patients completed the study and were included in the modified intention-to-treat analysis for the primary endpoint. After 12 months we noted no significant difference in the change in left ventricular mass between the placebo group and the losartan group (mean difference 1 g/m(2), 95% CI -3 to 6; p=0·60). A decrease in systolic blood pressure in the losartan group (from mean 127 mm Hg [SD 12] to 121 mm Hg [14]; p=0·0001) confirmed drug compliance; blood pressure did not decrease in the placebo group. Two (2%) patients, both in the placebo group, died from sudden cardiac death during follow-up. In the losartan group, one (1%) patient had angioedema, one (1%) had deterioration of renal function, and one (1%) had hyperkalaemia. Treatment was well tolerated by patients with left ventricular outflow obstruction at baseline. Our findings challenge the generally held view that angiotensin II receptor blockers reduce cardiac hypertrophy. Treatment with losartan was safe, suggesting that it can be used for other indications in patients with hypertrophic cardiomyopathy, irrespective of obstructive physiology. Additional studies are needed to assess the effect of angiotensin II receptor blockers in preclinical hypertrophic cardiomyopathy-eg, in genotype-positive but phenotype-negative individuals.

Safety and efficacy of drug-induced sleep endoscopy using a probability ramp propofol infusion system in patients with severe obstructive sleep apnea.

Drug-induced sleep endoscopy (DISE) uses sedative-hypnotics to induce moderate obstruction in sleep apnea patients, thereby facilitating anatomic assessment of obstructive physiology. Implementation of DISE with propofol requires a dosing strategy that reliably and efficiently produces obstruction while minimizing oxygen desaturation. The surgeon in a prospective study of transoral robotic resection of the tongue base enrolled 97 patients with obstructive sleep apnea confirmed by polysomnography who failed continuous positive airway pressure. All patients were screened by DISE. Propofol dose was determined using custom software written in MATLAB, which has been previously described. Studies were performed in an operating room with standard monitors and resuscitation equipment. No topical anesthesia was used, and no IV drugs other than propofol were used. All patients received 2 L/min supplemental oxygen via a nasal cannula placed in the mouth. After initiation of propofol sedation, a pediatric bronchoscope was positioned via the naris to observe the velopharynx. The sedation sequence was continued until the clinical end point of obstruction onset was noted. Observation of the pharynx was performed for a sufficient period to obtain images of the anatomic site(s) of obstruction. The infusion was then terminated. Statistical analysis was performed with MATLAB (MathWorks, version 2012b). Comparison of saturation nadirs between DISE and subject sleep studies was performed with both the paired and unpaired Student t test. The subject population was characterized by a median body mass index of 32.1 (interquartile range [IQR] 6.8) kg/m and apnea-hypopnea index of 48 (IQR 32). All patients demonstrated obstruction within the design variables. Obstruction was observed after 236 (±57.9) seconds at an estimated effect-site concentration of 4.2 ± 1.3 mcg/mL. The median saturation nadir during DISE was significantly higher (91.4% (IQR 5.1)) than that during standard sleep studies (81.0% [IQR 11.2], P < 0.0001). Ninety-five percent confidence intervals for correlations between DISE saturation nadir and body mass index, age, apnea-hypopnea index, or administered propofol dose included zero in all cases. A propofol infusion strategy that requires limited experience with propofol dose selection and only 1 pump dosing change reliably produced airway obstruction in patients with severe sleep apnea. Clinical obstruction was achieved faster than target-controlled infusion-based systems for similar procedures reported in the literature. The observed degree of oxygen desaturation in the model system was within a clinically acceptable range.

Evaluation of Apical Subtype of Hypertrophic Cardiomyopathy Using Cardiac Magnetic Resonance Imaging With Gadolinium Enhancement

Apical hypertrophic cardiomyopathy (HC) is an uncommon variant of HC. We sought to characterize cardiac magnetic resonance imaging (MRI) findings among apical HC patients. This was a retrospective review of consecutive patients with a diagnosis of apical HC who underwent cardiac MRI examinations at the Mayo Clinic (Rochester, MN) from August 1999 to October 2011. Clinical and demographic data at the time of cardiac MRI study were abstracted. Cardiac MRI study and 2-dimensional echocardiograms performed within 6months of the cardiac MRI were reviewed; 96 patients with apical HC underwent cardiac MRI examinations. LV end-diastolic and end-systolic volumes were 130.7 ± 39.1ml and 44.2 ± 20.9ml, respectively. Maximum LV thickness was 19 ± 5mm. Hypertrophy extended beyond the apex into other segments in 57 (59.4%) patients. Obstructive physiology was seen in 12 (12.5%) and was more common in the mixed apical phenotype than the pure apical (19.3 vs 2.6%, p= 0.02). Apical pouches were noted in 39 (40.6%) patients. Late gadolinium enhancement (LGE) was present in 70 (74.5%) patients. LGE was associated with severe symptoms and increased maximal LV wall thickness. In conclusion, cardiac MRI is well suited for studying the apical form of HC because of difficulty imaging the cardiac apex with standard echocardiography. Cardiac MRI is uniquely suited to delineate the presence or absence of an apical pouch and abnormal myocardial LGE that may have implications in the natural history of apical HM. In particular, the presence of abnormal LGE is associated with clinical symptoms and increased wall thickness.

Progression and Prognostic Indicators of Bronchial Disease in Children with Sickle Cell Disease

The pulmonary complications of sickle cell disease (SCD) are a leading cause of morbidity and mortality (MacLean et al. Am J Respir Crit Care Med 178:1055-1059, 2008; Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; National Heart, Lung, and Blood Institute, 2009). Despite this recognition, predictive markers of lung dysfunction progression remain elusive (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Platt et al. N Engl J Med 330:1639-1644, 1994; Caboot et al. Curr Opin Pediatr 20:279-287, 2008; Field et al. Am J Hematol 83:574-576, 2008; Shirlo et al. Peadiatr Respir Review 12:78-82, 2011). This study was designed describe the longitudinal progression and identify specific markers that influence bronchial disease in SCD. A retrospective, chart review of 89 patients with SCD was conducted. All patients underwent spirometry in conjunction with body plethysmography as part of routine care. Eleven lung function variables were assessed, five of which were selected to establish patterns of normal, obstructive, restrictive, or mixed obstructive-restrictive physiology (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Field et al. Am J Hematol 83:574-576, 2008). In the unadjusted model, forced expiratory volume in one second (FEV1)% of predicted trended downward with age, while total lung capacity (TLC)% of predicted showed a bimodal distribution and carbon monoxide diffusion capacity corrected for hemoglobin (DLCOcor)% of predicted remained stable. Adjusting for acute chest syndrome (ACS) episodes, medication status, and growth velocity (GV), the final model demonstrated that the downward trend between FEV1% of predicted with age was further influenced by the latter two factors. Initial decline in FEV1% of predicted is associated with worsening pulmonary dysfunction over time. Independent of ACS episodes, the factors most influential on the progression of FEV1% predicted include the introduction of medications as well as the promotion of adequate prepubertal growth. Efforts to ensure normal prepubertal GV and treatment with bronchodilators, such as short-acting beta(2) agonists and inhaled corticosteroids (ICS), should be considered at an early age to delay progression of pulmonary dysfunction.

Septal reduction therapies in hypertrophic cardiomyopathy: comparison of surgical septal myectomy and alcohol septal ablation

Abstract Left ventricular outflow tract obstruction, either resting or labile, occurs in approximately 70% of patients with hypertrophic cardiomyopathy and is a major cause of symptoms. In patients with obstructive physiology and medically refractory symptoms, septal myectomy and alcohol septal ablation reduce the left ventricular outflow tract gradient and improve symptoms. Myectomy is more effective at gradient reduction compared with ablation, with lower need for subsequent pacemaker implantation. However, cohort studies and meta-analyses have shown short-term mortality and post-procedural functional classes are similar between procedures. In many centers alcohol septal ablation case volumes have surpassed myectomy. There remains significant controversy regarding choice of myectomy or ablation. This review describes the two septal reduction procedures, examines the available comparative data for clinical outcomes and discusses clinical considerations when selecting myectomy or ablation.