Manometry Optimized Positive Expiratory Pressure (MOPEP) in Excessive Dynamic Airway Collapse (EDAC).

BACKGROUND: Positive expiratory pressure(PEP) breathing modalities are commonly prescribed in obstructive lung diseases, however practical methods of airway pressures(AP) quantification for therapeutic efficacy are lacking. Excessive dynamic airway collapse(EDAC) is characterized by expiratory central airway collapse leading to dyspnea and poor quality of life(QoL), with limited therapeutic options. PURPOSE: To measure AP and exertional dyspnea in EDAC patients during normal breathing and with use of pursed-lip breathing(PLB), nasal PEP device(nPEP), and oral-PEP valve(oPEP) during rest and exercise using an Esophageal Manometer. METHODS: EDAC patients exercised on a bicycle ergometer sequentially using normal breathing, PLB, nPEP, and oPEP for five-minute intervals. AP's were measured by continuous topographic upper airway manometry. Pre- and post-exercise BORG dyspnea scores were recorded and QoL measured with the St. George's respiratory questionnaire(SGRQ-C). The most effective and patient-preferred PEP modality was prescribed for daily activities and SGRQ-C repeated after one week. RESULTS: Three women with symptomatic EDAC participated. Expiratory laryngopharyngeal AP's during exercise with normal breathing, PLB, nPEP and oPEP in patient-1 were 1.7, 14, 4.5, and 7.3 mmHg, in patient-2; 2.3, 8, 8.3, and 12 mmHg, and in patient-3; 1, 15, unobtainable, and 9 mmHg, respectively. Maximal reduction in BORG scores occurred with PLB in patient 1 and with oPEP in patients 2 and 3. After 1 week mean SGRQ-C scores declined by 17-points. CONCLUSIONS: Upper airway manometry directly measures laryngopharyngeal pressures during rest and exercise and can be used to select and optimize PEP breathing techniques to improve respiratory symptoms in EDAC patients.

A Tablet-Based Multimedia Education Tool Improves Provider and Subject Knowledge of Inhaler Use Techniques.

BACKGROUND: Although inhaled medications are effective therapies for COPD, many patients and providers use them incorrectly. METHODS: We recruited providers who prescribe inhalers or teach inhaler technique and assessed their use of metered-dose inhalers (MDIs), various dry powder inhalers (DPIs), and Respimat using predefined checklists. Then they watched tablet-based multimedia educational videos that demonstrated correct inhaler technique by a clinical pharmacist with teach-back from a patient and were re-evaluated. We also recruited patients with COPD and assessed their use of their prescribed inhalers and then retested them after 3-6 months. Baseline and follow-up respiratory symptoms were measured by the COPD Assessment Test. RESULTS: Fifty-eight providers and 50 subjects participated. For all providers, correct inhaler technique (reported as percentage correct steps) increased after the videos: MDI without a spacer (72% vs 97%) MDI with a spacer (72% vs 96%), formoterol DPI (50% vs 94%), mometasone DPI (43% vs 95%), tiotropium DPI (73% vs 99%), and Respimat (32% vs 93%) (before vs after, P < .001 for all comparisons). Subjects also improved their inhaler use technique after viewing the educational videos: MDI without a spacer (69% vs 92%), MDI with a spacer (73% vs 95%), and tiotropium DPI (83% vs 96%) (before vs after, P < .001 for all comparisons). The beneficial effect of this educational intervention declined slightly for subjects but was durably improved after several months. COPD Assessment Test scores did not demonstrate any change in respiratory symptoms. CONCLUSIONS: A tablet-based inhaler education tool improved inhaler technique for both providers and subjects. Although this intervention did show durable efficacy for improving inhaler use by patients, it did not reduce their respiratory symptoms.

Long acting muscarinic antagonists for the treatment of chronic obstructive pulmonary disease: a review of current and developing drugs.

INTRODUCTION: Long acting muscarinic receptor antagonists (LAMA) reverse airflow obstruction by antagonizing para-sympathetic bronchoconstricting effects within the airways. For years, tiotropium, has been the cornerstone LAMA for chronic obstructive pulmonary disease (COPD) management. Recently, new agents, aclidinium bromide, glycopyrronium bromide, and umeclidinium bromide, have been developed and introduced into clinical practice. Areas covered: This article reviews the clinical efficacy and adverse effects of currently available LAMAs in COPD treatment as well as developing LAMAs in early clinical trials and preclinical studies (V0162, TD-4208, CHF 5407, AZD9164, AZD8683, bencycloquidium). In addition, a new class of molecule that combines muscarinic antagonist and ß2-adrenergic properties (MABA) is described and current developmental progress discussed (GSK-961081, THRX-200495). Expert opinion: Future key areas for developing drugs for the management of COPD include prolonged duration of action, optimal delivery systems, synergistic combinations with other drugs, maximization of benefits and minimization of adverse effects. The development of new LAMA and MABA molecules provides exciting progress towards simpler and more effective COPD management.

Phosphodiesterase 4 inhibitors for the treatment of chronic obstructive pulmonary disease: a review of current and developing drugs.

INTRODUCTION: Phosphodiesterase (PDE) inhibitors modulate lung inflammation and cause bronchodilation by increasing intracellular cyclic adenosine 3', 5'-monophosphate in airway smooth muscle and inflammatory cells. Roflumilast is the only approved PDE-4 inhibitor (PDE4I) for use in chronic obstructive pulmonary disease (COPD). Its beneficial clinical effects occur preferentially in patients with chronic bronchitis and frequent COPD exacerbations. Use of roflumilast as adjunctive or alternate therapy to other COPD medications reduces exacerbations and modestly improves lung function. AREAS COVERED: This article reviews the current role of PDE4I in COPD treatment emphasizing roflumilast's clinical efficacy and adverse effects. This article also reviews developing PDE4Is in early clinical trials and in preclinical studies. EXPERT OPINION: After decades of research in drug development, PDE4Is are a welcomed addition to the COPD therapeutic armamentarium. In its current clinical role, the salubrious clinical effects of PDE4I in reducing exacerbations and stabilizing the frequent exacerbator phenotype have to be cautiously balanced with numerous adverse effects. Developing drugs may provide similar or better clinical benefits while minimizing adverse effects by changing the mode of drug delivery to inhaled formulations, combining dual PDE isoenzyme inhibitors (PDE1/4I and PDE3/4I) and by forming hybrid molecules with other bronchodilators (muscarinic receptor antagonist/PDE4I and ß2-agonist/PDE4I).

Native Pulmonic Valve Endocarditis due to Mycobacterium fortuitum: A Case Report and Literature Review.

Endocarditis secondary to Mycobacterium fortuitum is a rare entity often involving prosthetic valves and rarely native valves. Pulmonic valve endocarditis secondary to any organism is rare. We report the first case of native pulmonic valve endocarditis secondary to M. fortuitum and a literature review of native valve M. fortuitum endocarditis.

Massive gastrointestinal hemorrhage as a complication of the Flexi-Seal fecal management system.

Use of the Flexi-Seal fecal management system, a safe and effective means of fecal diversion in patients with fecal incontinence and diarrhea, can be associated with rare, life-threatening complications. For example, a critically ill patient had 2 episodes of massive rectal bleeding associated with use of the system that required transfusion of blood products. Hemorrhage was controlled during the first episode by angiography with selective coil embolization; the second required colonoscopy with suture ligation of the affected lesion. A literature review revealed 9 other cases that were managed endoscopically, surgically, or with angiography. Although none of the patients died, they experienced obvious complications that required transfusion of blood products, endoscopy, surgery, use of conscious sedation or general anesthesia, angiography, and exposure to intravenous contrast material. Patients receiving therapeutic doses of anticoagulation and antiplatelet drugs, which may precipitate or aggravate hemorrhaging, are particularly at risk for complications with the Flexi-Seal system.

Therapeutic paralysis in veterans with COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a common disorder of Veterans that causes significant morbidity and mortality. To measure Veterans' perceptions about COPD, the effect of COPD on their lives and health, and their needs for improved health, we performed a postal survey. METHODS: 3263 Veterans with a diagnosis of COPD who received care at the Cincinnati Veterans Affairs Medical Center in 2008 were stratified into quintiles by Veterans Health Administration-associated COPD healthcare cost and uniformly sampled. RESULTS: 493 of 1000 surveys (49%) were completed and returned. COPD had different effects on respondents in top and bottom quintiles (highest and lowest COPD-related cost) for: knowledge of COPD diagnosis (89% vs. 73%, p = 0.03); activities affected by breathing, including work (69% vs. 45%), recreation (85% vs. 62%), change in living arrangements (36% vs 16%), and increased need for help (54% vs. 25%) (p < 0.05 for all comparisons); emotional effect of respiratory symptoms, including depression (53% vs. 30%), fear (41% vs. 15%), and helplessness (49% vs. 24%) (p < 0.05 for all comparisons). 91% of Veterans were prescribed inhalers and one-quarter had difficulties using them. 25% of Veterans did nothing when they had symptoms of an exacerbation. CONCLUSIONS: COPD has profound effects on Veterans' breathing related activities and generates many negative emotions. Primary care providers are critical in conveying the diagnosis of COPD and providing information about the disease and its management. Veterans with COPD adhere poorly to their medications, and report little instruction about COPD or its management.

Diverticular disease associated with inflammatory bowel disease-like colitis: a systematic review.

PURPOSE: Diverticular-associated colitis significantly overlaps clinically with primary inflammatory bowel disease. However, the clinical and the pathologic features of diverticular-associated colitis suggest that it is a distinct clinical entity. METHODS: We performed a systematic review by use of multiple health care databases and gray literature, following predefined inclusion and exclusion criteria to determine the clinical, endoscopic, and pathologic features of diverticular-associated colitis, and recurrence rates following medical and surgical treatment. RESULTS: Two hundred twenty-seven participants were selected from 18 eligible studies, including our own patients (n = 13). The average age of disease onset was 64 years. The typical symptoms included tenesmus, hematochezia, and diarrhea. One hundred sixty-three of the 227 patients in these studies were classified as having diverticular-associated colitis, of which 142 were managed medically. Twenty-eight patients eventually required an operation. One-quarter (37 of 163) of the patients had recurrence of symptoms with an average follow-up time of three years. CONCLUSIONS: Diverticular-associated colitis is a distinct entity that presents with segmental colitis and a variety of clinical, endoscopic, and pathologic features. Diverticular-associated colitis should be considered in the presence of recurrent symptoms after resection for diverticulitis.

Inflammatory bowel disease and African Americans: a systematic review.

BACKGROUND: Inflammatory bowel disease (IBD) is comprised of Crohn's disease (CD) and ulcerative colitis (UC). There are conflicting reports on whether African Americans have a more severe disease course, presentation, and more frequent extraintestinal manifestations (EIM). We examined the precise nature of this relationship by conducting a systematic review. METHODS: Using predefined inclusion criteria we searched multiple healthcare databases and Grey literature. Eight reports met the inclusion criteria. Using the parameters as defined in the Montreal classification and the presence or absence of EIM, we compared IBD in African Americans and Caucasians. RESULTS: Over 2000 IBD cases were pooled from 8 reports with African Americans comprising 17%. African Americans and Caucasians had similar distribution of types of IBD, with CD being more common than UC in both groups (CD 76% versus 68% and UC 24% versus 32%, respectively). With respect to CD, both groups presented with nonstricturing and nonpenetrating disease behavior (55% versus 41%) more frequently and had similar rates of ileocolonic disease location (42% versus 38%), and presence of perianal disease (26% versus 29%). In UC patients, proctitis was the most frequent initial presentation in both races. Joint complications were the most frequent EIM in both African Americans (52%) and Caucasians (60%). CONCLUSIONS: This study dispels the commonly held views that African Americans with IBD generally have more colonic disease, more severe disease behavior, and more perianal disease than Caucasians. African Americans also have similar variety and frequency of EIMs as compared to Caucasians.

Frequency and surgical management of chronic complications related to pelvic radiation.

HYPOTHESIS: Refractory complications from pelvic radiotherapy often require surgical treatment. Their management may be dictated by the primary tumor, radiation dose, and type and combination of radiation injuries, and may require transient diversion in most cases to guarantee good outcomes. DESIGN: Retrospective 10-year cohort analysis compared with statewide epidemiologic data. PATIENTS: During a 10-year period, 14 791 patients in Kentucky were treated with pelvic radiotherapy. Forty-eight were referred to a university colorectal surgical unit for evaluation of refractory radiotherapy complications that had failed conservative medical management. MAIN OUTCOME MEASURES: Epidemiologic statewide data were compared with hospital data regarding the treatment and outcome of patients with refractory pelvic radiotherapy complications. RESULTS: Twenty-five patients had received radiotherapy for colorectal carcinoma, 10 for prostate cancer, 7 for carcinoma of the cervix, and 6 for other tumors. Patients presented with 1 or more complications, including radiation enteritis (60%), strictures (53%), fistulae (17%), nonhealing wounds (15%), and de novo cancers in radiated fields (10%). Low anastomotic strictures (10%) were initially treated by dilation under sedation. Six patients (12%) ultimately required permanent diversion. All radiation-induced fistulae required an operation. CONCLUSIONS: Determining the proper treatment requires careful judgment and assessment of the degree and type of injury, patient anatomy, and sphincter function. Patients presenting with colorectal anastomotic and primary bowel strictures as their main complication had the best results, while most patients with severe radiation enteritis and very distal strictures required permanent diversion.