Yardstick for managing cough, part 2: In children.

Nationwide statistics in the United States and Australia reveal that cough of undifferentiated duration is the most common complaint for which patients of all ages seek medical care in the ambulatory setting. Management of chronic cough is one of the most common reasons for new patient visits to respiratory specialists. Because symptomatic cough is such a common problem and so much has been learned about how to diagnose and treat cough of all durations but especially chronic cough, this 2-part yardstick has been written to review in a practical way the evidence-based guidelines most of which have been developed from high-quality systematic reviews on how best to manage cough of all durations in adults, adolescents, and children. Chronic cough in children is often benign and self-limiting. Using established and validated protocols and specific pointers (clues in history, findings on examination) can aid the clinician in identifying causes when present and improve outcomes. In this manuscript, part 2 of the 2-part series, we provide evidence-based, expert opinion recommendations on the management of chronic cough in the pediatric patient (<14 years of age).

Yardstick for managing cough, part 1: In adults and adolescent patients older than 14 years of age.

Nationwide statistics in the United States and Australia reveal that cough of undifferentiated duration is the most common complaint for which patients of all ages seek medical care in the ambulatory setting. Management of chronic cough is one of the most common reasons for new patient visits to pulmonologists. Because symptomatic cough is such a common problem and so much has been learned about how to diagnose and treat cough of all durations but especially chronic cough, this 2-part yardstick has been written to review in a practical way the latest evidence-based guidelines most of which have been developed from recent high quality systematic reviews on how best to manage cough of all durations in adults, adolescents, and children. In this manuscript, part 1 of the 2-part series, we provide evidence-based, and expert opinion recommendations on the management of chronic cough in adult and adolescent patients (>14 years of age).

Prevalence and test characteristics of national health safety network ventilator-associated events.

OBJECTIVES: The primary aim of the study was to measure the test characteristics of the National Health Safety Network ventilator-associated event/ventilator-associated condition constructs for detecting ventilator-associated pneumonia. Its secondary aims were to report the clinical features of patients with National Health Safety Network ventilator-associated event/ventilator-associated condition, measure costs of surveillance, and its susceptibility to manipulation. DESIGN: Prospective cohort study. SETTING: Two inpatient campuses of an academic medical center. PATIENTS: Eight thousand four hundred eight mechanically ventilated adults discharged from an ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The National Health Safety Network ventilator-associated event/ventilator-associated condition constructs detected less than a third of ventilator-associated pneumonia cases with a sensitivity of 0.325 and a positive predictive value of 0.07. Most National Health Safety Network ventilator-associated event/ventilator-associated condition cases (93%) did not have ventilator-associated pneumonia or other hospital-acquired complications; 71% met the definition for acute respiratory distress syndrome. Similarly, most patients with National Health Safety Network probable ventilator-associated pneumonia did not have ventilator-associated pneumonia because radiographic criteria were not met. National Health Safety Network ventilator-associated event/ventilator-associated condition rates were reduced 93% by an unsophisticated manipulation of ventilator management protocols. CONCLUSIONS: The National Health Safety Network ventilator-associated event/ventilator-associated condition constructs failed to detect many patients who had ventilator-associated pneumonia, detected many cases that did not have a hospital complication, and were susceptible to manipulation. National Health Safety Network ventilator-associated event/ventilator-associated condition surveillance did not perform as well as ventilator-associated pneumonia surveillance and had several undesirable characteristics.

Managing Chronic Cough Associated with Idiopathic Pulmonary Fibrosis - Will Nalbuphine Fill an Unmet Need?

In this issue of NEJM Evidence, Maher et al.1 report the results of a randomized, controlled, 22-day treatment crossover trial comparing the antitussive effect of extended-release nalbuphine, an opioid agonist-antagonist, with placebo in a cohort of patients with definite or probable idiopathic pulmonary fibrosis (IPF). In this small, short-term trial of 38 evaluable patients, the active drug was associated with a 75.1% reduction in daytime objective cough frequency (the primary outcome) compared with a 22.6% reduction in placebo-treated patients, yielding a substantial and statistically significant 52.5 percentage point placebo-adjusted change from baseline.

Cough Hypersensitivity Syndrome: Why Its Use Is Inappropriate in Children.

In children and adults, chronic cough is a common symptom presenting to health professionals worldwide. It is internationally accepted that children with chronic cough should be managed with pediatric specific management guidelines. The newly proposed clinical entity of 'cough hypersensitivity syndrome' has gained significant attention in adult literature. Given the significant differences between childhood and adult chronic cough, including in respiratory physiology and anatomy, and cough sensitivity, we address the suitability of the use of cough hypersensitivity syndrome in children. We explore these differences between childhood and adult chronic cough, explain what cough hypersensitivity is and highlight why the term cough hypersensitivity syndrome should not be used in children.

Testing an aflatoxin B1 gene signature in rat archival tissues.

Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 µg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and ß-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced tumors. We conclude that an evaluation of gene signatures in archival tissues can be an important toxicological tool for evaluating critical molecular events associated with chemical exposures.

Get fit with the Grizzlies: a community-school-home initiative to fight childhood obesity led by a professional sports organization.

BACKGROUND: Professional sports organizations in the United States have notable celebrity status, and several teams have used this "star power" to collaborate with local schools toward the goal of affecting childhood obesity (e.g., NFL Play 60). Program effectiveness is unknown owing to the absence of comprehensive evaluations for any of these initiatives. In 2006, the Memphis Grizzlies, the city's National Basketball Association (NBA) franchise, launched "Get Fit with the Grizzlies," a 6-week, curricular addition focusing on nutrition and physical activity for the 4th and 5th grades in Memphis City Schools. The health-infused mini-unit was delivered by the physical education teachers during their classes. National and local sponsors whose business objectives matched the "Get Fit" objectives were solicited to fund the program. Here we highlight the program evaluation results from the first year of "Get Fit" and the Journal of School Health article. However, the "Get Fit" program has now taken place in Memphis area schools for 5 years. During the 2010-11 school-year, "Get Fit" evolved into a new program called "Healthy Home Court" with Kellogg's as the primary sponsor. "Healthy Home Court" included the original fitness part of the program and added a breakfast component at high schools where data indicated great need. Kellogg's sponsored special "carts" with healthy breakfast options (i.e., fruit, protein bars) for students to grab and eat. This program matched their existing program "Food Away from Home." Research supports the objectives of these programs and has shown that breakfast consumption can have a positive impact on academic achievement, behavior in school, and overall health status. METHOD: Survey research employed over the first 4 years measured health knowledge acquisition and health behavior change using a matched pre/post test design (n=2210) in randomly chosen schools (n=18) from all elementary schools in the Memphis area. McNemar's test for significance (<05) was applied to measure correct answers pre and post. Also, breakfast attendance numbers were observed for intervention high schools and compared with breakfast attendance numbers from control high schools. RESULTS: Analyses confirmed that, from the first year through this past one (2010-11), there was significant health knowledge acquisition and health behavior improvement at post-intervention. Breakfast numbers matched these findings. Also, exit polling that took place at one intervention high school indicated the students attending the breakfast assembly gained knowledge and positively changed attitudes regarding the academic and health benefits of eating a healthy breakfast. CONCLUSIONS: This community-school-home initiative using a professional team's celebrity platform is largely overlooked by school districts and should be considered as an effective way to confront childhood obesity.

Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel.

Background: Cough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity. Objective: The aim of this study was to establish items and domains that would inform development of a new cough severity instrument. Methods: Three focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity. Results: The patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, and provided an additional subdomain related to cough triggers. The final conceptual framework comprised 51 items in the following domains: urge-to-cough sensations (subdomains: frequency and intensity) and cough symptom (subdomains: triggers, control, frequency, fit/bout duration, intensity, quality and associated features/sequelae). Conclusions: Consensus findings from patients and international experts established domains of urge-to-cough and cough symptom with associated subdomains and relevant items. The results support item generation and content validity for a novel patient-reported outcome measure for use in health research and clinical practice.

Hospital mortality, length of stay, and preventable complications among critically ill patients before and after tele-ICU reengineering of critical care processes.

CONTEXT: The association of an adult tele-intensive care unit (ICU) intervention with hospital mortality, length of stay, best practice adherence, and preventable complications for an academic medical center has not been reported. OBJECTIVE: To quantify the association of a tele-ICU intervention with hospital mortality, length of stay, and complications that are preventable by adherence to best practices. DESIGN, SETTING, AND PATIENTS: Prospective stepped-wedge clinical practice study of 6290 adults admitted to any of 7 ICUs (3 medical, 3 surgical, and 1 mixed cardiovascular) on 2 campuses of an 834-bed academic medical center that was performed from April 26, 2005, through September 30, 2007. Electronically supported and monitored processes for best practice adherence, care plan creation, and clinician response times to alarms were evaluated. MAIN OUTCOME MEASURES: Case-mix and severity-adjusted hospital mortality. Other outcomes included hospital and ICU length of stay, best practice adherence, and complication rates. RESULTS: The hospital mortality rate was 13.6% (95% confidence interval [CI], 11.9%-15.4%) during the preintervention period compared with 11.8% (95% CI, 10.9%-12.8%) during the tele-ICU intervention period (adjusted odds ratio [OR], 0.40 [95% CI, 0.31-0.52]). The tele-ICU intervention period compared with the preintervention period was associated with higher rates of best clinical practice adherence for the prevention of deep vein thrombosis (99% vs 85%, respectively; OR, 15.4 [95% CI, 11.3-21.1]) and prevention of stress ulcers (96% vs 83%, respectively; OR, 4.57 [95% CI, 3.91-5.77], best practice adherence for cardiovascular protection (99% vs 80%, respectively; OR, 30.7 [95% CI, 19.3-49.2]), prevention of ventilator-associated pneumonia (52% vs 33%, respectively; OR, 2.20 [95% CI, 1.79-2.70]), lower rates of preventable complications (1.6% vs 13%, respectively, for ventilator-associated pneumonia [OR, 0.15; 95% CI, 0.09-0.23] and 0.6% vs 1.0%, respectively, for catheter-related bloodstream infection [OR, 0.50; 95% CI, 0.27-0.93]), and shorter hospital length of stay (9.8 vs 13.3 days, respectively; hazard ratio for discharge, 1.44 [95% CI, 1.33-1.56]). The results for medical, surgical, and cardiovascular ICUs were similar. CONCLUSION: In a single academic medical center study, implementation of a tele-ICU intervention was associated with reduced adjusted odds of mortality and reduced hospital length of stay, as well as with changes in best practice adherence and lower rates of preventable complications.

The legacy of fear: is fear impacting fatal and non-fatal drowning of African American children?

African American children's rates for fatal and non-fatal drowning events are alarmingly elevated, with some age groups having three times the rate as compared to White peers. Adequate swimming skills are considered a protective agent toward the prevention of drowning, but marginalized youth report limited swimming ability. This research examined minority children's and parents/caregivers' fear of drowning as a possible variable associated with limited swimming ability. Results confirmed that there were significant racial differences concerning the fear of drowning, and adolescent African American females were notably more likely to fear drowning while swimming than any other group. The "fear of drowning" responses by parents/ caregivers of minority children were also significantly different from their White counterparts.

Global Physiology and Pathophysiology of Cough: Part 1: Cough Phenomenology - CHEST Guideline and Expert Panel Report.

The purpose of this state-of-the-art review is to update the American College of Chest Physicians 2006 guideline on global physiology and pathophysiology of cough. A review of the literature was conducted using PubMed and MEDLINE databases from 1951 to 2019 and using prespecified search terms. We describe the basic phenomenology of cough patterns, behaviors, and morphological features. We update the understanding of mechanical and physiological characteristics of cough, adding a contemporary view of the types of cough and their associated behaviors and sensations. New information about acoustic characteristics is presented, and recent insights into cough triggers and the patient cough hypersensitivity phenotype are explored. Lastly, because the clinical assessment of patients largely focuses on the duration rather than morphological features of cough, we review the morphological features of cough that can be measured in the clinic. This is the first of a two-part update to the American College of Chest Physicians 2006 cough guideline; it provides a more global consideration of cough phenomenology, beyond simply the mechanical aspects of a cough. A greater understanding of the typical features of cough, and their variations, may allow a more informed interpretation of cough measurements and the clinical relevance for patients.

Global Physiology and Pathophysiology of Cough: Part 2. Demographic and Clinical Considerations: CHEST Expert Panel Report.

BACKGROUND: Cough characteristics vary between patients, and this can impact clinical diagnosis and care. The purpose of part two of this state-of-the-art review is to update the American College of Chest Physicians (CHEST) 2006 guideline on global physiology and pathophysiology of cough. STUDY DESIGN AND METHODS: A review of the literature was conducted using PubMed and MEDLINE databases from 1951 to 2019 using prespecified search terms. RESULTS: We describe the demographics of typical patients with cough in the clinical setting, including how cough characteristics change across age. We summarize the effect of common clinical conditions impacting cough mechanics and the physical properties of mucus on airway clearance. INTERPRETATION: This is the second of a two-part update to the 2006 CHEST cough guideline; it complements part one on basic phenomenology of cough by providing an extended clinical picture of cough along with the factors that alter cough mechanics and efficiency in patients. A greater understanding of the physiology and pathophysiology of cough will improve clinical management.

Predicting the hepatocarcinogenic potential of alkenylbenzene flavoring agents using toxicogenomics and machine learning.

Identification of carcinogenic activity is the primary goal of the 2-year bioassay. The expense of these studies limits the number of chemicals that can be studied and therefore chemicals need to be prioritized based on a variety of parameters. We have developed an ensemble of support vector machine classification models based on male F344 rat liver gene expression following 2, 14 or 90 days of exposure to a collection of hepatocarcinogens (aflatoxin B1, 1-amino-2,4-dibromoanthraquinone, N-nitrosodimethylamine, methyleugenol) and non-hepatocarcinogens (acetaminophen, ascorbic acid, tryptophan). Seven models were generated based on individual exposure durations (2, 14 or 90 days) or a combination of exposures (2+14, 2+90, 14+90 and 2+14+90 days). All sets of data, with the exception of one yielded models with 0% cross-validation error. Independent validation of the models was performed using expression data from the liver of rats exposed at 2 dose levels to a collection of alkenylbenzene flavoring agents. Depending on the model used and the exposure duration of the test data, independent validation error rates ranged from 47% to 10%. The variable with the most notable effect on independent validation accuracy was exposure duration of the alkenylbenzene test data. All models generally exhibited improved performance as the exposure duration of the alkenylbenzene data increased. The models differentiated between hepatocarcinogenic (estragole and safrole) and non-hepatocarcinogenic (anethole, eugenol and isoeugenol) alkenylbenzenes previously studied in a carcinogenicity bioassay. In the case of safrole the models correctly differentiated between carcinogenic and non-carcinogenic dose levels. The models predict that two alkenylbenzenes not previously assessed in a carcinogenicity bioassay, myristicin and isosafrole, would be weakly hepatocarcinogenic if studied at a dose level of 2 mmol/kg bw/day for 2 years in male F344 rats; therefore suggesting that these chemicals should be a higher priority relative to other untested alkenylbenzenes for evaluation in the carcinogenicity bioassay. The results of the study indicate that gene expression-based predictive models are an effective tool for identifying hepatocarcinogens. Furthermore, we find that exposure duration is a critical variable in the success or failure of such an approach, particularly when evaluating chemicals with unknown carcinogenic potency.

Tricuspid regurgitation: contemporary management of a neglected valvular lesion.

Right-sided cardiac valvular disease has traditionally been considered less clinically important than mitral or aortic valve pathology. However, detectable tricuspid regurgitation (TR) is common and recent data suggest that significant TR can lead to functional impairment and reduced survival, particularly in patients with concomitant left-sided valvular disease. The tricuspid valve is a complex anatomical structure and advances in three dimensional echocardiography and cardiac MRI have contributed to a greater understanding of tricuspid valve pathology. These imaging techniques are invaluable in determining the aetiology and severity of TR, and provide an assessment of right ventricular function and pulmonary artery pressure. TR is more prevalent in women and those with a history of myocardial infarction and heart failure. It also occurs in about 10% of patients with rheumatic heart disease. Chronic severe TR may have a prolonged clinical course culminating in the development of fatigue and poor exercise tolerance due to a reduced cardiac output. Approximately 90% of cases of TR are secondary to either pulmonary hypertension or intrinsic right ventricular pathology and about 10% are due to primary tricuspid valve disease. Primary causes such as Ebstein's anomaly, rheumatic disease, myxomatous changes, carcinoid syndrome, endomyocardial fibrosis, and degenerative disease have characteristic morphological features readily identifiable by echocardiography. Ascertaining an accurate right ventricular systolic pressure is important in separating primary from secondary causes as significant TR with a pressure <40 mm Hg implies intrinsic valve disease. Cardiac MRI may be indicated in those with inadequate echocardiographic images and is also the gold standard for the evaluation of right ventricular function and morphology. The assessment of leaflet morphology, annular dimensions, and pulmonary artery pressure are particularly important for determining subsequent management. Along with appropriate treatment of the underlying cause of TR and pulmonary hypertension, management guidelines indicate a move towards more aggressive treatment of TR. In those undergoing left-sided valve surgery, tricuspid valve repair is universally recommended in the presence of severe coexistent TR; in those with isolated severe TR, surgery is recommended in the presence of symptoms or progressive right ventricular dilatation or dysfunction.

Life-Threatening and Non-Life-Threatening Complications Associated With Coughing: A Scoping Review.

BACKGROUND: This is an update of the section on complications that are associated with coughing in the 2006 CHEST cough guidelines that addresses two aims: (1) to systematically identify and thematically categorize the diverse complications of cough by providing a guide for future studies and (2) to identify gaps in the literature for future research. RESEARCH QUESTION: What are the potential complications that are associated with the act of coughing that have been reported in infants, children, adolescents, and adults? STUDY DESIGN AND METHODS: A scoping review was performed with the use of PubMed and SCOPUS databases that were searched from their beginning until September 6, 2019. RESULTS: Two hundred forty-seven publications met our inclusion criteria. To these, we added 38 articles from the 2006 complications paper that were not identified in the literature search plus the paper itself for a final total of 286 publications that formed the basis of this review. Since 2006, three new categories of complications have been reported: ear, nose and throat; disease transmission; and laboratory testing. Multiple additional complications that fall outside of these three categories have also been identified and included in the following categories: cardiovascular, constitutional symptoms, dermatologic, GI, genitourinary, musculoskeletal, neurologic, ophthalmologic, psychosocial/quality of life, and respiratory. Not previously highlighted is that some of the complications led to serious morbidity that included death, especially in patients with comorbid conditions, and potentially resulted in harm to others when cough resulted in a motor vehicle accident. INTERPRETATION: Our work identified a large number of cough complications that we thematically categorized primarily by organ system so that future studies of each system or each complication can be conducted. The gap in the literature that future studies should address is to identify the frequency of the complications and the strength of their association with cough. Only then will one be able to describe the findings in a manner that allows specific recommendations for avoiding these complications. In the meantime, patients with cough should be evaluated and treated according to evidence-based guidelines to mitigate or prevent the myriad of potential complications that are associated with coughing.