Muhammad Ahsan Zafar

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 β2-agonist/PDE4I).

Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases

The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogeneous processes characterised by the presence of multiple, thin-walled, air-filled spaces within the pulmonary parenchyma [1]. The differential diagnosis of DCLDs includes lymphangioleiomyomatosis (LAM), follicular bronchiolitis (FB), lymphocytic interstitial pneumonia (LIP), Birt–Hogg–Dubé syndrome (BHD), pulmonary Langerhans cell histiocytosis (PLCH), amyloidosis, light chain deposition disease, cystic metastases, infectious entities such as Pneumocystis, and other aetiologies [2]. Bronchiectasis and bullous changes seen in chronic obstructive pulmonary disease can also produce high-resolution computed tomography (HRCT) patterns that mimic the DCLDs. Correct diagnosis of diffuse cystic lung diseases is established in most cases by critical review of HRCT features http://ow.ly/NvrCc

Connecting resident education to patient outcomes: the evolution of a quality improvement curriculum in an internal medicine residency.

As part of the Accreditation Council for Graduate Medical Education’s Next Accreditation System, residency programs must connect resident-physician education to improved patient care outcomes. Residency training programs, however, face multiple obstacles in doing so. Results from residency quality improvement (QI) curricula tend to show improvement in simple process-based measures but not in more complex outcomes of care such as diabetes or blood pressure control. In this article, the authors describe the evolution of their QI educational program for internal medicine residents at the University of Cincinnati Medical Center within the structure of a novel training model called the Ambulatory Long Block. They discuss a resident-run project that led to reduced rates of patients with uncontrolled diabetes as an example of improvement in outcome measures. Despite favorable results from that particular resident group, the successful intervention did not spread practice-wide. Using this example, they detail the phases of evolution and lessons learned from their curriculum from 2006 to 2014 within a framework of previously published general principles for successful QI education, including those of exemplary care and learning sites. Successful programs require leadership, faculty expertise and mentorship, data management, learner buy-in, and patient engagement. Their experience will hopefully be of help to others as they attempt to simultaneously improve care and education. Further research and innovation are needed in this area, including optimizing strategies for strengthening resident-driven projects through partnership with nursing, allied health, and longitudinally engaged faculty members.

Orbital aspergillus infection mimicking a tumour: a case report

A 14-year-old male presented to the neurosurgical clinic with swelling just above the right eye which had been growing slowly for the last eight years. The swelling first appeared following a non-penetrating trauma eight years ago. On examination it was a non-tender, non-erythematous, firm, round swelling causing marked proptosis and diplopia on downward gaze only. The visual acuity was intact. MRI showed an intraorbital, extraconal mass isointense on T1 and hypointense on T2 imaging. A diagnosis of orbital tumor was made. A white, friable mass consistent with meningioma was resected. However histopathology report later showed it to be an Aspergilloma. The patient was successfully treated with anti-fungal medicine and was disease-free at one year follow-up.

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

ABSTRACT 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 β2-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.

Reliable adherence to a COPD care bundle mitigates system-level failures and reduces COPD readmissions: a system redesign using improvement science

Background Readmissions of chronic obstructive pulmonary disease (COPD) have devastating effects on patient quality-of-life, disease progression and healthcare cost. Effective interventions to reduce COPD readmissions are needed. Objectives Reduce 30-day all-cause readmissions by (1) creating a COPD care bundle that addresses care delivery failures, (2) using improvement science to achieve 90% bundle adherence. Setting An 800-bed academic hospital in Ohio, USA. The COPD 30-day all-cause readmission rate was 22.7% from August 2013 to September 2015. Method We performed a cross-sectional study of COPD 30-day readmissions from October 2014 to March 2015 to identify care delivery failures. We interviewed readmitted patients with COPD to identify their needs after discharge. A multidisciplinary team created a care bundle designed to mitigate system failures. Using a quasi-experimental study and ‘Model for Improvement’, we redesigned care delivery to improve bundle adherence. We used statistical process control charts to analyse bundle adherence and all-cause 30-day readmissions. Results Cross-sectional review of the index (first-time) admissions revealed COPD was the most common readmission diagnosis and identified 42 system-level failures. The most prevalent failures were deficient inhaler regimen at discharge, late or non-existent follow-up appointments, and suboptimal discharge instructions. Patient interviews revealed confusing discharge instructions, especially regarding inhaler use. The COPD care-bundle components were: (1) appropriate inhaler regimen, (2) 30-day inhaler supply, (3) inhaler education on the device available postdischarge, (4) follow-up within 15 days (5) standardised patient-centred discharge instructions. The adherence to completing bundle components reached 90% in 5.5 months and was sustained. The COPD 30-day readmission rate decreased from 22.7% to 14.7%. Patients receiving all bundle components had a readmission rate of 10.9%. As a balancing measure for the targeted reduction in readmission rate, we assessed length of stay, which did not change (4.8 days before vs 4.6 days after; p=0.45). Conclusion System-level failures and unmet patient needs are modifiable risks for readmissions. Development and reliable implementation of a COPD care bundle that mitigates these failures reduced COPD readmissions.

Update on ultra-long-acting β agonists in chronic obstructive pulmonary disease

Introduction: For the last two decades, long-acting β agonists (LABAs) have been a cornerstone in the management of chronic obstructive pulmonary disease (COPD). They relax airway smooth muscle and augment expiratory airflow, which reduces hyperinflation and improves dyspnea, functional capacity and quality of life. In recent years, Indacaterol, a LABA with an ultra-long duration of action (ultra-LABA), which only requires once-daily dosing, was approved by the FDA. The clinical efficacy of indacaterol is comparable, and, in some aspects better, than the currently available LABAs. Areas covered: This article reviews the pharmacological properties, clinical efficacy, safety and potential role of the ultra-LABAs in COPD management. Expert opinion: Ultra-LABAs are effective bronchodilators with a prolonged duration of action. By decreasing dosing frequency, ultra-LABAs potentially may improve respiratory medication adherence, which is associated with better survival and less healthcare utilization. In addition to their salubrious benefits, β agonists may produce untoward effects. Increased mortality and hospitalizations among patients with left ventricular heart failure, who were treated with β agonists, has caused concern about their use in patients with COPD and heart disease. Further experience and testing will determine the optimal role of ultra-LABAs in the management of COPD.

Massive Subcutaneous Emphysema from a Complicated Intubation

1Pulmonary, Critical Care and Sleep Medicine Division, University of Cincinnati College of Medicine, Cincinnati, Ohio; 2Gastroenterology and Hepatology Division, Baylor College of Medicine, Houston, Texas, USA Correspondence: Dr Muhammad A Zafar, Pulmonary, Critical Care and Sleep Medicine Division, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, Ohio 45229, USA. Telephone 513-827-2345, e-mail zafarmd@ucmail.uc.edu A 58-year-old woman with morbid obesity, diabetes and rheumatoid arthritis was admitted to the intensive care unit with septic shock due to an infected knee that required surgical irrigation and drainage. Postoperatively, she developed hypercarbic respiratory failure necessitating emergent reintubation. Three hours later, a tense swelling with crepitus was noticed on her neck and chest. A computed tomography scan of her chest revealed massive subcutaneous emphysema, pneumomediastinum and pneumothorax due to a tracheal laceration (Figures 1 to 3). She was emergently taken to the operative room. Flexible bronchoscopy showed a posterior tracheal perforation just above the carina. Right thoracotomy revealed a 2 cm tear in the membranous trachea extending toward the right main stem bronchus, which was repaired. After a prolonged stay in the intensive care unit, the patient died due to multiorgan failure and gastrointestinal bleeding. iMages in respiratory Medicine

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. APs were measured by continuous topographic upper airway manometry. Pre- and post-exercise BORG dyspnea scores were recorded and QoL measured with the St. Georges 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 APs 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.