Philip Alapat

Genome-wide association study of smoking behaviours in patients with COPD

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within cholinergic receptors, nicotinic, alpha 3/5 (CHRNA3/CHRNA5; eg, p=0.00011 for SNP rs1051730) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6; eg, p=2.78×10−5 for a non-synonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in DBH was significantly (p=0.015) associated with smoking cessation. Conclusion The authors identified two candidate regions associated with age at smoking initiation in patients with COPD. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviours of patients with COPD.

Validation of Automatic Wheeze Detection in Patients with Obstructed Airways and in Healthy Subjects

Computerized lung-sound analysis is a sensitive and quantitative method to identify wheezing by its typical pattern on spectral analysis. We evaluated the accuracy of the VRI, a multi-sensor, computer-based device with an automated technique of wheeze detection. The method was validated in 100 sound files from seven subjects with asthma or chronic obstructive pulmonary disease and seven healthy subjects by comparison of auscultation findings, examination of audio files, and computer detection of wheezes. Three blinded physicians identified 40 sound files with wheezes and 60 sound files without wheezes. Sensitivity and specificity were 83% and 85%, respectively. Negative predictive value and positive predictive value were 89% and 79%, respectively. Overall inter-rater agreement was 84%. False positive cases were found to contain sounds that simulate wheezes, such as background noises with high frequencies or strong noises from the throat that could be heard and identified without a stethoscope. The present findings demonstrate that the wheeze detection algorithm has good accuracy, sensitivity, specificity, negative predictive value and positive predictive value for wheeze detection in regional analyses with a single sensor and multiple sensors. Results are similar to those reported in the literature. The device is user-friendly, requires minimal patient effort, and, distinct from other devices, it provides a dynamic image of breath sound distribution with wheeze detection output in less than 1 minute.

Multicenter implementation of a consensus-developed, evidence-based, spontaneous breathing trial protocol.

Objective:Evidence-based practice recommendations abound, but implementation is often unstructured and poorly audited. We assessed the ability of a peer network to implement an evidence-based best practice protocol and to measure patient outcomes. Design:Consensus definition of spontaneous breathing trial followed by implementation in eight academic medical centers. Setting:Six medical, two surgical, and two combined medical/surgical adult intensive care units among eight academic medical centers. Study Population:Patients initiating mechanical ventilation through an endotracheal tube during a 12-wk interval formed the study population. Interventions:Adoption and implementation of a common spontaneous breathing trial protocol across multiple intensive care units. Measurements and Main Results:Seven hundred five patients had 3,486 safety screens for conducting a spontaneous breathing trial; 2072 (59%) patients failed the safety screen. Another 379 (11%) patients failed a 2-min tolerance screen and 1,122 (34%) patients had a full 30–120 min spontaneous breathing trial performed. Seventy percent of eligible patients were enrolled. Only 55% of passing spontaneous breathing trials resulted in liberation from mechanical ventilatory support before another spontaneous breathing trial was performed. Conclusions:Peer networks can be effective in promoting and implementing evidence-based best practices. Implementation of a best practice (spontaneous breathing trial) may be necessary for, but by itself insufficient to achieve, consistent and timely liberation from ventilator support.

Association of adverse perinatal outcomes with screening measures of obstructive sleep apnea

Objective:This prospective observational study explored the association of hypertensive disorders of pregnancy and small-for-gestational age with obstructive sleep apnea (OSA) as determined by screening measures for OSA and sleep studies.Study Design:Two symptom-based screening questionnaires, the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), were administered to enroll 1509 gravidae. Screen-positive subjects were referred for polysomnography. The primary outcome was the occurrence of either gestational hypertension or preeclampsia. Generalized linear models (GLM) were used to estimate the relative risks of associations.Result:One thousand one hundred and fifty-seven subjects were available for outcomes analysis. Screening positive on the BQ was positively associated with hypertensive disorders in GLM models (adjusted relative risk=1.90, 95% confidence interval 1.52 to 2.37).Conclusion:In this large prospective trial, GLM modeling suggests that the BQ but not the ESS demonstrated significant association with measured adverse pregnancy outcomes, and specific items predicted these outcomes better than others. However, causative association of BQ with OSA cannot be assumed.

Toxicology in the Critical Care Unit

Toxicologic conditions are encountered in critically ill patients due to intentional or unintentional misuse of or exposure to therapeutic or illicit drugs. Additionally, toxicities related to medical interventions may develop in hospitalized patients. This review focuses on recent developments in the field of critical care toxicology. Early interventions to decrease absorption or enhance elimination of toxins have limited value. Specific interventions to manage toxicities due to analgesics, sedative-hypnotics, antidepressants, antipsychotics, cardiovascular agents, alcohols, carbon monoxide, and cholinergic agents are reviewed. Hospital-acquired toxicities due to methemoglobinemia, propylene glycol, and propofol should be recognized and treated. The clinician is continually required to incorporate clinical judgment along with available scientific data and clinical evidence to determine the best therapy for toxicologic conditions.

Evaluation of Obstructive Lung Disease with Vibration Response Imaging

As optimal treatment and prognosis differ between asthma and COPD, a new diagnostic approach to differentiating between the two disorders would be clinically desirable. We evaluated the utility of vibration response imaging in differentiating between asthma and COPD. Sixty-six subjects with asthma or COPD were recorded, before and after the administration of a short-acting bronchodilator, using a computerized lung sound analysis device. Gray-scale images of breath sound distribution in the lungs, quantitative data in breath sound graphs (timing, amplitude) and automatic crackle and wheeze detection programs were used to differentiate between asthma and COPD subjects. Imaging data were compared with the clinical diagnosis, made by the standard methods (medical history, physical examination, and spirometric indices). Blinded evaluation of images demonstrated a significantly higher rate of improvement in image dynamics, shape and overall improvement following bronchodilator in subjects with asthma compared with those with COPD. Quantitative data showed distinct patterns in timing and amplitude for these two pathologies. Combined analyses based on qualitative image evaluation and quantitative data demonstrated an overall 85% accuracy (84% for asthma, 86% for COPD) in differentiating between asthma and COPD. Combined qualitative and quantitative evaluations of lung sounds are quite sensitive in distinguishing between lung sound recordings of COPD and asthma individuals. Lung sound features of synchronization in timing and intensity provide objective data that may further differentiate these two airway disorders.

Management of Obstructive Sleep Apnea in the Indigent Population A Deviation of Standard of Care

Comprehensive management of patients with obstructive sleep apnea (OSA) typically is managed best via a multidisciplinary approach, involving otolaryngologists, sleep psychologists/psychiatrists, pulmonologists, neurologists, oral surgeons, and sleep trained dentists. By utilizing these resources, one could fashion a treatment individualized to the patient, giving rise to the holistic phrase of “personalized medicine.” Unfortunately, in situations and environments with limited resources, the treatment options in an otolaryngologist’s armamentarium are restricted—typically to continuous positive airway pressure (CPAP) versus sleep surgery. However, a recent patient encounter highlighted here shows how a hospital’s reimbursement policy effectively dictated a patient’s medical management to sleep surgery. This occurred although the current gold standard for the initial treatment of OSA is CPAP. Changing the course of medical/surgical management by selectively restricting funding is a cause of concern, especially when it promotes patients to choose a treatment option that is not considered the current standard of care.

Acid Base Disorders

Acid–base disorders present some of the most challenging problems in the care of critically ill patients. They alter physiologic function and contribute to morbidity and mortality. Proper management of these disorders is not possible without the understanding of blood gas interpretation and basic acid–base balance physiology.