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Background/objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may involve the kidney, respiratory tract, skin, or central and peripheral nervous system. Reports of interstitial lung disease (ILD) in AAV (AAV-ILD) have been increasing. Methods We reviewed the medical records of all patients with AAV-ILD between January 1, 2007, and December 31, 2017, and compared their pulmonary involvement to patients with idiopathic pulmonary fibrosis (IPF). Results We identified 24 patients with AAV-ILD: 14 with microscopic polyangiitis, 8 with granulomatosis with polyangiitis, and 2 with eosinophilic granulomatosis with polyangiitis. Perinuclear or myeloperoxidase ANCA was present in 16 cases (66.7%), whereas cytoplasmic or proteinase 3 ANCA was positive in 8 (33.3%). Usual interstitial pneumonia (UIP) was seen in 11 (45.8%), probable UIP in 1 (4.2%), indeterminate UIP in 2 (8.3%), and an alternate diagnosis in 10 (41.7%), and was further characterized as chronic hypersensitivity pneumonitis-like pattern seen in 6 (25%), nonspecific interstitial pneumonia-like pattern in 3 (12.5%), and cryptogenic organizing pneumonia-like pattern in 1 (4.2%). Forced vital capacity and diffusing capacity declined over time in patients with AAV-ILD. When compared with the IPF cohort, patients with AAV-ILD had intermediate survival and speed of lung function decline (3-year survival in AAV-ILD group was 94% vs 69% in IPF). Conclusions Antineutrophil cytoplasmic antibody-associated vasculitis ILD is a progressive and potentially fatal condition. Although most cases in the literature are associated with p-ANCA and positive myeloperoxidase, we found that a third of patients had c-ANCA or granulomatosis with polyangiitis. Our cohort adds experience in this rare manifestation of AAV.

Purpose Gastro-oesophageal reflux disease (GORD) is commonly thought to play an important role in chronic cough and patients are often empirically treated with acid suppression therapy. We sought to investigate the response rate to acid suppression treatment in patients with and without heartburn attending two specialist cough clinics. Methods A retrospective review of 558 consecutive patients referred to two specialist cough clinics was performed (UK and USA). Patients who were treated with acid suppression were included and their documented response to treatment was collected. Binary logistic regression was used to ascertain the value of reported heartburn in predicting the response of chronic cough to acid suppression therapy. Results Of 558 consecutive referrals, 238 patients were excluded due to missing data or cough duration of Conclusion In specialist cough clinics, few patients report a response of their chronic cough to acid suppression therapy. Nonetheless, heartburn is a useful predictor substantially increasing the likelihood of benefit.

Objectives Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. Methods This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. Results In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). Conclusions This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive fibrotic interstitial lung disease often resulting in death over several years. Prediction of disease course or survival remains of keen interest for clinicians and patients though a commonly used test or tool remain elusive. Areas covered: We undertook a comprehensive review of the published literature highlighting prognostic indicators and predictors of survival in IPF. Baseline and longitudinal clinical, functional, histopathologic, and radiologic findings have been extensively studied as prognostic predictors, both individually and in composite models. Recent approaches include automated quantifiable radiologic scoring, circulating biomarkers, and genetic polymorphisms or abnormalities. This review highlights individual and composite predictors and their relative utility in clinical practice and research studies. Expert opinion: There is a growing body of knowledge highlighting readily available individual and composite predictors of outcome, though none have come to the forefront for common clinical use. Recent advances include quantitative imaging analysis, circulating serologic markers, and genetic testing, which may be more standardized and less prone to lead-time bias or related complications and comorbidities.

Lung involvement in connective tissue diseases is associated with substantial morbidity and mortality, most commonly in the form of interstitial lung disease, and can occur in any of these disorders. Patterns of interstitial lung disease in patients with connective tissue disease are similar to those seen in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis. It may be difficult to distinguish between the 2 ailments, particularly when interstitial lung disease presents before extrapulmonary manifestations of the underlying connective tissue disease. There are important clinical implications in achieving this distinction. Given the complexities inherent in the management of these patients, a multidisciplinary evaluation is needed to optimize the diagnostic process and management strategies. The aim of this article was to summarize an approach to diagnosis and management based on the opinion of experts on this topic.

Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a β-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute. Clinical trial registered with www.clinicaltrials.gov (NCT 04193878).

Objective To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. Methods We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. Results A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19–directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. Conclusion Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

BACKGROUND: The clinical benefits of cardiopulmonary rehabilitation are extensive, including improvements in health-related quality of life, emotional condition, physical function, and overall mortality. The COVID-19 pandemic continues to have a negative impact on center-based cardiopulmonary rehabilitation. Justifiable concern exists that the exercise-related increase in pulmonary ventilation within the rehabilitation classes may lead to the generation of infectious respiratory particles. RESEARCH QUESTION: Is cardiopulmonary rehabilitation while wearing a procedural mask a particle-generating procedure? STUDY DESIGN AND METHODS: Data were collected prospectively at a cardiopulmonary rehabilitation facility with all patients wearing a procedural mask. Small (0.3-4.9 µm) and large (5-10 µm) particle generation was quantified using a light-scattering particle counter. Data were analyzed by time, exertion level, and number of participants. RESULTS: A total of 24 distinct patients attended two or more of the cardiopulmonary rehabilitation classes tested. Most of the patients were men (n = 16 [67%]) and were in rehabilitation because of cardiac disease. During the cardiopulmonary rehabilitation class, small and large micrometer-size particles increased with increasing class size. In classes with four patients or more, a significant increase was found from ambient levels in both small (four patients, P < .01; and five patients, P < .01) and large (four patients, P < .01; and five patients, P < .01) particle count that peaked at about 35 to 40 min during each class. INTERPRETATION: Using an airborne particle counter, we found significant exercise-related increases in both small and large micrometer-size particle generation during cardiopulmonary rehabilitation classes, with larger class sizes (ie, more patients), despite participants wearing a procedural mask.

Introduction Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux-a prerequisite of aspiration), and pulmonary function in patients with IPF. Methods We prospectively recruited 35 patients with IPF (aged 53-75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment. Results Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux (P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = -0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = -0.478; P = 0.098) and number of proximal events (r = -0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = -0.520; P = 0.039) and inspiratory LESP (r = -0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008). Discussion We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs.

Background Pulmonary disease is a potentially serious yet underdiagnosed complication of Sjogren’s syndrome, the second most common autoimmune rheumatic disease. Approximately 16% of patients with Sjogren’s demonstrate pulmonary involvement with higher mortality and lower quality of life. Research Question Clinical practice guidelines for pulmonary manifestations of Sjogren’s were developed by the Sjogren’s Foundation after identifying a critical need for early diagnosis and improved quality and consistency of care. Study Design and Methods A rigorous and transparent methodology was followed according to American College of Rheumatology guidelines. The Pulmonary Topic Review Group (TRG) developed clinical questions in the PICO (Patient, Intervention, Comparison, Outcome) format and selected literature search parameters. Each article was reviewed by a minimum of two TRG members for eligibility and assessment of quality of evidence and strength of recommendation. Guidelines were then drafted based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale and data extraction tables were submitted to a Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. Results The literature search revealed 1,192 articles, of which 150 qualified for consideration in guideline development. Of the original 85 PICO questions posed by the TRG, 52 recommendations were generated. These were then reviewed by the Consensus Expert Panel and 52 recommendations were finalized, with a mean agreement of 97.71% (range, 79%-100%). The recommendations span topics of evaluating Sjogren’s patients for pulmonary manifestations and assessing, managing, and treating upper and lower airway disease, interstitial lung disease, and lymphoproliferative disease. Interpretation Clinical practice guidelines for pulmonary manifestations in Sjogren’s will improve early identification, evaluation, and uniformity of care by primary care physicians, rheumatologists, and pulmonologists. Additionally, opportunities for future research are identified.

STUDY OBJECTIVES: The objectives of this study were to assess the effect of obstructive sleep apnea (OSA) on the risk of acute pulmonary embolism (PE), hospital outcomes including mortality, and PE recurrence. METHODS: We retrospectively enrolled adult patients, admitted to Mayo Clinic Hospital in Rochester, Minnesota, within a 5-year period (2009–2013). We compared frequency of PE, hospital mortality, and secondary outcomes in patients with OSA versus patients without OSA. We assessed risk of PE recurrence in relation to compliance with OSA therapy. RESULTS: Of 25,038 patients, 3,184 (13%) had OSA and 283 (1.1%) experienced PE. Frequency of PE in patients with and without OSA was 2.4% versus 0.9% (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.9–3.3; P < .001). OSA was independently associated with increased risk of PE after adjusting for demographics and comorbidities (OR, 1.44; 95% CI, 1.07–1.9; P = .017). Adjusted hospital mortality was increased in patients with PE (OR, 2.88; 95% CI, 1.7–4.9; P < .001) but not in patients with OSA (OR, 0.98; 95% CI, 0.7–1.4, P = .92). OSA was not a significant determining factor for mortality in patients who experienced a PE (OR, 0.56; 95% CI, 0.1.1–2.78; P = .47), adjusting for demographics, PE severity, and Charlson comorbidity index. Adjusted risk of PE recurrence was greater in patients with OSA compared with patients without OSA (OR, 2.21; 95% CI, 1.05–4.68; P < .04). The patients compliant with OSA therapy had a lower rate of PE recurrence (16% vs 32%; P = not significant). CONCLUSIONS: Although OSA significantly increases risk of acute PE occurrence and recurrences, related hospital mortality was not greater in patients with OSA compared with those without OSA. OSA therapy might have a modifying effect on PE recurrence. CITATION: Secken ZI, Helmi H, Weister TJ, Lee A, Festic E. Acute pulmonary embolism in patients with obstructive sleep apnea: frequency, hospital outcomes, and recurrence. J Clin Sleep Med. 2020;16(7):1029–1036.

Aspiration is a syndrome with variable respiratory manifestations that span acute, life-threatening illnesses, such as acute respiratory distress syndrome, to chronic, sometimes insidious, respiratory disorders such as aspiration bronchiolitis. Diagnostic testing is limited by the insensitivity of histologic testing, and although gastric biomarkers for aspiration are increasingly available, none have been clinically validated. The leading mechanism for microaspiration is thought to be gastroesophageal reflux disease, largely driven by the increased prevalence of gastroesophageal reflux across a variety of respiratory disorders, including chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, and chronic cough. Failure of therapies targeting gastric acidity in clinical trials, in addition to increasing concerns about both the overuse of and adverse events associated with proton pump inhibitors, raise questions about the precise mechanism and causal link between gastroesophageal reflux and respiratory disease. Our review summarizes key aspiration syndromes with a focus on reflux-mediated aspiration and highlights the need for additional mechanistic studies to find more effective therapies for aspiration syndromes.

Background Clinical differentiation of fibrotic hypersensitivity pneumonitis (f-HP) remains challenging given variable and overlapping presentations with other fibrotic interstitial lung disease (f-ILD). Objective We derived a multivariable model for predicting histopathologic f-HP to better inform multidisciplinary team discussion (MDD) diagnosis, particularly when biopsy may be unsafe or cannot be achieved. Methods Patients with histopathologically-defined f-HP and other overlapping f-ILD were reviewed for distinguishing clinical and radiological variables. Using elastic net logistic regression, a penalized regression approach to minimize overfitting, a clinical model built on non-invasive assessments was derived for the prediction of histopathologic f-HP. This model was then validated in an independently derived external cohort from three sites. Results The derivation and validation cohorts consisted of 248 (84 cHP and 164 other f-ILD) and 157 (82 f-HP and 75 other f-ILD) histopathologically-defined patients, respectively (total study N = 405). Variables retained from the elastic net model included age in years (regression coefficient 0.033), male sex (−1.109), positive exposure history (1.318), percent predicted forced vital capacity (−0.021), radiologic peribronchovascular axial ILD distribution (0.199), mid (−0.22) or lower lobe (−0.839) craniocaudal or patchy (0.287) ILD distribution, upper (1.188) or equivalent upper and lower lobe (0.237) traction bronchiectasis, mosaic attenuation (1.164), and centrilobular nodules (2.045). Bias corrected AUC was 0.84 (standard error = 0.02) for the derivation cohort and 0.80 (CI 0.73–0.87) for the validation cohort. Conclusions This multivariable model demonstrated good predictive performance for delineating histopathologically-defined f-HP from other f-ILD as a means of avoiding or justifying biopsy and supporting MDD diagnostic confidence.

Background The Coronavirus pandemic has a high mortality rate in patients that are mechanically ventilated, which has led to an ever increasing interest in noninvasive forms of oxygenation. The use of these devices has the theoretical risk of increased exposure risk because of possible particulate generation. This study aimed to quantify the particulate generation associated with different oxygen devices. Methods This was a prospective single center study conducted during September 2020 using ten healthy adult volunteers. Testing was conducted in a negative pressure hospital room using a light scattering particle counter. The oxygen devices used were a nasal cannula, an OxyMask™, a non-rebreathing mask, and a high flow system. Particle measurements were obtained at baseline in the room and then with each oxygen delivery device and pre-specified oxygen flow rates. These measurements were obtained different distances from the volunteer with their mouth open. A Wilcoxon/Kruskal-Wallis test was performed on each separate oxygen modality with all flow rates as one model. Results The particle concentrations were slightly non-significantly increased with the OxyMask™ and non-rebreathing mask at the closest distance measured. As the distance increased, these counts decreased closer to ambient levels. The nasal cannula and high flow nasal cannula particle counts were not significantly different from ambient measurements at either distance. Conclusion Nasal cannula, OxyMask™, non-rebreathing mask, and high flow oxygen did not generate any additional aerosols or droplets above a baseline room measurement, but further studies are necessary to determine infectious risk.

Objectives The tricuspid annular plane systolic excursion (TAPSE) is a validated measure of right ventricular function; however, the apical echocardiographic window varies and has limitations in intensive care unit (ICU) patients receiving mechanical ventilation or those with underlying disease and air entrapment. We aimed to evaluate the subcostal echocardiographic assessment of tricuspid annular kick (SEATAK) as an alternative to TAPSE in critically ill patients. Methods To measure SEATAK, we obtained the subcostal inferior vena cava view and used M-mode to measure excursion of the tricuspid annulus (kick). Analysis was performed with JMP for Bland-Altman and Spearman correlations. Results We evaluated 45 patients, 26 (57.8%) of whom were women, with a mean age of 60.8 years. We were not able to obtain the apical view to measure TAPSE in 8.9% of the patients. In contrast, SEATAK was measured in all patients. The mean SEATAK and TAPSE were 1.62 cm and 1.93 cm, respectively, with a mean pairwise difference of −0.26 cm (95% CI: −0.19 to −0.35), with the SEATAK value being lower than TAPSE. The overall correlation was strong and significant (ρ = .86, P=.03). The graphical correlation was maintained between TAPSE and SEATAK and the degree of RVF. Conclusion In patients presenting with RVF in the ICU (or in situations where the apical echocardiographic view is suboptimal for tricuspid annular assessment), SEATAK can be an alternative to TAPSE. Further research is needed to validate and determine the sensitivity and specificity of SEATAK for RVF prognostication.

Gastro-oesophageal reflux is associated with a wide range of respiratory disorders, including asthma, isolated chronic cough, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cystic fibrosis. Reflux can be substantial and reach the proximal margins of the oesophagus in some individuals with specific pulmonary diseases, suggesting that this association is more than a coincidence. Proximal oesophageal reflux in particular has led to concern that microaspiration might have an important, possibly even causal, role in respiratory disease. Interestingly, reflux is not always accompanied by typical reflux symptoms, such as heartburn and/or regurgitation, leading many clinicians to empirically treat for possible gastro-oesophageal reflux. Indeed, costs associated with use of acid suppressants in pulmonary disease far outweigh those in typical GERD, despite little evidence of therapeutic benefit in clinical trials. This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease.

Background There is a need for improved clinical identification of hospitalized patients at risk of aspiration. We evaluated our novel phonetic test in a broad spectrum of patients at risk of aspiration in the ICU or intermediate care unit. Methods We prospectively enrolled 60 hospitalized patients with aspiration risk, between December 2009 and September 2011, who subsequently underwent audio-recorded three-component phonetic bedside evaluation. The recordings were scored by two blinded speech-language pathologists. The institutional dysphagia admission screening test was performed by a bedside nurse. The primary outcomes, dysphagia and aspiration, were assessed by a videofluoroscopic swallowing study, fiber-optic endoscopic evaluation of swallowing, or both. We assessed the short- and long-term clinical outcomes (length of stay, subsequent aspiration pneumonia and respiratory failure, survival) and how these were associated with the phonetic and swallow assessments. Results Statistically significant linear associations with dysphagia were noted for all three individual phonetic components. Also, there were statistically significant linear associations with aspiration for diadochokinesis ( P = .050) and consensus auditory-perceptual evaluation of voice ( P = .025). Diadochokinesis alone predicted dysphagia (area under the curve [AUC], 0.74; P = .001) and aspiration (AUC, 0.67; P = .012). Its predictive ability improved when combined with normalized dysphagia admission screening test results (AUC, 0.79; P = .001). The short- and long-term clinical outcomes were adversely affected by the worse phonetic/swallowing scores, although they were not statistically different. Conclusions Abnormal phonation among ICU and intermediate care unit patients is associated with dysphagia and aspiration. Future investigative efforts should uncover the most effective combination of evaluations for accurate bedside detection of dysphagia and aspiration risk in a broad spectrum of patients.

Goals: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD). Background: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure. Study: Patients post-LTx (n=48, 24 female; aged 20 to 73 y) completed high-resolution impedance manometry and 24-hour pH/impedance. Results: Patients who had undergone unilateral LTx were more likely to exhibit esophagogastric junction outflow obstruction (47% vs. 18%; P=0.046) and less likely to exhibit hypocontractility (0% vs. 21%; P=0.058) than those who had undergone bilateral LTx. Although the proportion of patients exhibiting gastroesophageal reflux was no different between groups (33% vs. 39%; P=0.505), those undergoing bilateral LTx were more likely to exhibit proximal reflux (8% vs. 37%; P=0.067). Univariate Cox proportion hazards regression analysis did not show a difference between unilateral versus bilateral LTx in the development of o-CLAD (hazard ratio=1.17; 95% confidence interval, 0.48-2.85; P=0.723). Conclusion: The type of LTx performed seems to lead to different risk factors for the development of o-CLAD. Physicians should be aware of these differences, as they may need to be taken into account when managing patient’s post-LTx.

Objectives Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that generally results in progressive decline in lung function. Despite advancement of pharmacological therapy for LAM, lung transplantation remains an important option for women with end-stage LAM. Methods Patients with LAM undergoing lung transplantation at the Mayo Clinic campuses in Rochester, Minnesota and Jacksonville, Florida since 1995 were retrospectively reviewed. Results Overall, 12 women underwent lung transplantation. Nine of 12 (75%) underwent double lung transplant. The mean age was 42 ± 8 years at the time of transplant. One patient (8%) had a chylothorax and 7 (58%) had recurrent pneumothoraces, 4 (33%) of which required pleurodesis. All had diffuse, cystic lung disease on chest CT consistent with LAM which was confirmed in the explant of all patients. The average length of ICU and hospital stays were 5 ± 4 and 19 ± 19 days, respectively. Mild to moderate anastomotic ischemia was evident in all patients but resolved with time. No patient was treated with sirolimus pre-transplant. Seven patients received sirolimus post-transplant; however, clinical benefit was documented in only 2 patients, 1 of which was treated for large retroperitoneal cysts with ureteral obstruction and another with persistent chylothorax and retroperitoneal lymphangioleimyomas. Five patients are deceased. The median survival by Kaplan–Meier analysis was 119 months with a median follow-up of 68 months (range 2–225 months). Conclusions Lung transplant remains a viable treatment for patients with end-stage LAM. The role of sirolimus peri-transplantation remains ill-defined.

In the Fluid and Catheter Treatment Trial (FACTT) of the National Institutes of Health Acute Respiratory Distress Syndrome Network, a conservative fluid protocol (FACTT Conservative) resulted in a lower cumulative fluid balance and better outcomes than a liberal fluid protocol (FACTT Liberal). Subsequent Acute Respiratory Distress Syndrome Network studies used a simplified conservative fluid protocol (FACTT Lite). The objective of this study was to compare the performance of FACTT Lite, FACTT Conservative, and FACTT Liberal protocols.Retrospective comparison of FACTT Lite, FACTT Conservative, and FACTT Liberal. Primary outcome was cumulative fluid balance over 7 days. Secondary outcomes were 60-day adjusted mortality and ventilator-free days through day 28. Safety outcomes were prevalence of acute kidney injury and new shock.ICUs of Acute Respiratory Distress Syndrome Network participating hospitals.Five hundred three subjects managed with FACTT Conservative, 497 subjects managed with FACTT Liberal, and 1,124 subjects managed with FACTT Lite.Fluid management by protocol.Cumulative fluid balance was 1,918 ± 323 mL in FACTT Lite, -136 ± 491 mL in FACTT Conservative, and 6,992 ± 502 mL in FACTT Liberal (p0.001). Mortality was not different between groups (24% in FACTT Lite, 25% in FACTT Conservative and Liberal, p = 0.84). Ventilator-free days in FACTT Lite (14.9 ± 0.3) were equivalent to FACTT Conservative (14.6 ± 0.5) (p = 0.61) and greater than in FACTT Liberal (12.1 ± 0.5, p0.001 vs Lite). Acute kidney injury prevalence was 58% in FACTT Lite and 57% in FACTT Conservative (p = 0.72). Prevalence of new shock in FACTT Lite (9%) was lower than in FACTT Conservative (13%) (p = 0.007 vs Lite) and similar to FACTT Liberal (11%) (p = 0.18 vs Lite).FACTT Lite had a greater cumulative fluid balance than FACTT Conservative but had equivalent clinical and safety outcomes. FACTT Lite is an alternative to FACTT Conservative for fluid management in Acute Respiratory Distress Syndrome.

Pulmonary aspiration is an important recognized cause of ARDS. Better characterization of patients who aspirate may allow identification of potential risks for aspiration that could be used in future studies to mitigate the occurrence of aspiration and its devastating complications.We conducted a secondary analysis of the Lung Injury Prediction Score cohort to better characterize patients with aspiration, including their potential risk factors and related outcomes.Of the 5,584 subjects at risk for ARDS and who required hospitalization, 212 (3.8%) presented with aspiration. Subjects who aspirated were likely to be male (66% vs 56%, P.007), slightly older (59 years vs 57 years), white (73% vs 61%, P = .0004), admitted from a nursing home (15% vs 5.9%, P.0001), have a history of alcohol abuse (21% vs 8%, P.0001), and have lower Glasgow Coma Scale (median, 13 vs 15; P.0001). Aspiration subjects were sicker (higher APACHE [Acute Physiology and Chronic Health Evaluation] II score), required more mechanical ventilation (54% vs 32%, P.0001), developed more moderate to severe ARDS (12% vs 3.8%, P.0001), and were twofold more likely to die in-hospital, even after adjustment for severity of illness (OR = 2.1; 95% CI, 1.2-3.6). Neither obesity nor gastroesophageal reflux was associated with aspiration.Aspiration was more common in men with alcohol abuse history and a lower Glasgow Coma Scale who were admitted from a nursing home. It is independently associated with a significant increase in the risk for ARDS as well as morbidity and mortality. Findings from this study may facilitate the design of future clinical studies of aspiration-induced lung injury.

SummaryIdiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown cause characterized by relentlessly progressive restrictive-ventilatory limitation, hypoxia, dyspnea, and cough. Both the incidence and prevalence of IPF appears to be increasing, with little impact on its dismal 3-year median survival, despite two decades of clinical trials. Increasingly recognized are the serious associated comorbid illnesses, including pulmonary hypertension, chronic obstructive pulmonary disease, gastroesophageal reflux disease, obstructive sleep apnea, obesity, lung cancer, and depression that further contribute to the substantial rise in the use of IPF-related healthcare resources. At present, lung transplantation remains the sole viable treatment for the few who qualify. Pharmacologic interventions targeting lung function and survival have remained largely disappointing, and very few investigations have specifically targeted comorbid conditions, symptoms, quality-of-life, and healthcare resource utilization. In reviewing the burden of illness associated with IPF, including the epidemiology, comorbidities, quality-of-life and the physical, psychosocial, and economic costs of this devastating disease, we hope to highlight some of the unmet medical needs associated with IPF, and encourage both public support and further investigations into these and other patient-centered outcomes and not just that of survival and lung function.

Targeted temperature management (TTM) may improve respiratory mechanics and lung inflammation in acute respiratory distress syndrome (ARDS) based on animal and limited human studies. We aimed to assess the pulmonary effects of TTM in patients with respiratory failure following cardiac arrest. Retrospective review of consecutive cardiac arrest cases occurring out of hospital or within 24 hours of hospital admission (2002-2012). Those receiving TTM (n=44) were compared with those who did not (n=42), but required mechanical ventilation (MV) for at least 4 days following the arrest. There were no between-group differences in age, gender, body mass index, APACHE II, or fluid balance during the study period. The TTM group had lower ejection fraction, Glasgow Coma Score, and more frequent use of paralytics. Matched data analyses (change at day 4 compared with baseline of the individual subject) showed favorable, but not statistically significant trends in respiratory mechanics endpoints (airway pressure, compliance, tidal volume, and PaO2/FiO2) in the TTM group. The PaCO2 decreased significantly more in the TTM group, as compared with controls (-12 vs. -5 mmHg, p=0.02). For clinical outcomes, the TTM group consistently, although not significantly, did better in survival (59% vs. 43%) and hospital length of stay (12 vs. 15 days). The MV duration and Cerebral Performance Category score on discharge were significantly lower in the TTM group (7.3 vs. 10.7 days, p=0.04 and 3.2 vs. 4, p=0.01). This small retrospective cohort suggests that the effect of TTM ranges from equivalent to favorable, compared with controls, for the specific respiratory and clinical outcomes in patients with respiratory failure following cardiac arrest.

Objective: To address clinical concern regarding the use of inhaled corticosteroids (ICSs) and the risk for pneumonia, particularly among patients with chronic obstructive pulmonary disease (COPD) and asthma. Patients and Methods: A multicentered prospective cohort of patients admitted to the hospital from March 1, 2009, through August 31, 2009, with pneumonia or another risk factor for acute respiratory distress syndrome was analyzed to determine the risk for pneumonia requiring hospitalization among patients taking ICSs. The adjusted risk (odds ratio [OR]) for developing pneumonia because of ICSs was determined in a multiple logistic regression model. Results: Of the 5584 patients in the cohort, 495 (9%) were taking ICSs and 1234 (22%) had pneumonia requiring hospitalization. In univariate analyses, pneumonia occurred in 222 (45%) of the patients on ICSs vs 1012 (20%) in those who were not (OR, 3.28; 95% CI, 2.71-3.96; P

One of the most controversial issues in the development and treatment of acute respiratory distress syndrome (ARDS) is the effect of systemic corticosteroids (SCS). Physiologically, exposure to infectious or noninfectious insults elicits a host defense response aimed at containing and destroying the injurious agents via activation of inflammation, coagulation, and tissue repair pathways (1). In ARDS, dysregulated inflammation from either direct or indirect stimulus leads to a disruption of the alveolar-capillary membrane resulting in edema and filling of the pulmonary lobules with the protein-rich neutrophilic exudate (1, 2). Animal studies appear to support a protective role of exogenous SCS on lung function: dexamethasone alleviated meconium-induced airway hyperreactivity and attenuated endotoxin-induced lung injury by inhibition of inducible nitric oxide expression at the very early stage of ARDS (3, 4). However, studies investigating the role of SCS in humans yielded equivocal results. Trials incorporating high doses of methylprednisolone in mechanically ventilated patients at high risk for ARDS (5), patients with established ARDS (6, 7), or patients just diagnosed with sepsis (8, 9) mostly showed no benefit. Others, however, reported improvements (10), particularly with the use of lower doses of corticosteroids in earlier stages of ARDS (11, 12) and even in management of unresolving ARDS (13). Despite extensive research into management of ARDS and the use of protective modes of ventilation, overall associated hospital and ICU mortality remains high (14). Therefore, the task of the U.S. Critical Illness and Injury Trials Group: Lung Injury Prevention Study investigators has been to identify modifiable risks for ARDS and to seek strategies to prevent its occurrence. Given encouraging results of trials that used low-dose cortico-steroid administration early in the course of ARDS, we hypothesized that patients who take SCS prior to hospital admission might be protected against the development of ARDS.

Background Airway pepsin has been increasingly used as a potentially sensitive and quantifiable biomarker for gastric-to-pulmonary aspiration, despite lack of validation in normal control subjects. This study attempts to define normal levels of airway pepsin in adults and distinguish between pepsin A (exclusive to stomach) and pepsin C (which can be expressed by pneumocytes). Methods We performed a prospective study of 51 otherwise healthy adult patients undergoing elective extremity orthopedic surgery at a single tertiary-care academic medical center. Lower airway samples were obtained immediately following endotracheal intubation and just prior to extubation. Total pepsin and pepsin A concentrations were directly measured by an enzymatic activity assay, and pepsin C was subsequently derived. Pepsinogen/pepsin C was confirmed by Western blot analyses. Baseline characteristics were secondarily compared. Results In all, 11 (22%; 95% CI=9.9%–33%) had detectable airway pepsin concentrations. All 11 positive specimens had pepsin C, without any detectable pepsin A. Pepsinogen/pepsin C was confirmed by Western blot analyses. In a multivariate logistic regression, men were more likely to have airway pepsin (OR, 12.71, P = .029). Conclusions Enzymatically active pepsin C, but not the gastric-specific pepsin A, is frequently detected in the lower airways of patients who otherwise have no risk for aspiration. This suggests that nonspecific pepsin assays should be used and interpreted with caution as a biomarker of gastropulmonary aspiration, as pepsinogen C potentially expressed from pneumocytes may be detected in airway samples.

Introduction Patients at risk for microaspiration during elective intubation often receive cricoid pressure in the hopes of mitigating such risk. However, there is scarce evidence to either support or reject this practice. The objective of this investigation was to assess the effect of cricoid pressure on microaspiration and to inform the potential feasibility of conducting a larger, more definitive clinical trial. Methods This was a pilot randomized clinical trial set in the operating rooms of a tertiary referral hospital between August and October of 2014. Patients with risk factors for microaspiration (obesity, gastroesophageal reflux disease, or diabetes) were enrolled. The patients were randomized to either cricoid pressure or no cricoid pressure during induction of anesthesia with endotracheal intubation. Immediately after intubation, a sample of lower airway secretions was collected and analyzed for pepsin A. Main results A total of 95 patients were evaluated, randomized and completed the study protocol. 46 were randomized to cricoid pressure and 49 to no cricoid pressure. Seven patients crossed-over treatment arms. A total of 18 (19.6%) patients met the pre-defined criteria for microaspiration. In both the intention-to-treat and per-protocol analyses, there were no statistically significant differences in the rate of microaspiration [OR (95% CI)] = 1.39 (0.49-3.92) and 1.30 (0.44-3.86), respectively. Conclusions Utilizing pepsin A as a biomarker of aspiration, this pilot clinical trial did not find evidence for a reduced rate of aspiration or adverse clinical events with the administration of cricoid pressure during elective endotracheal intubation of patients with risk factors for microaspiration.

Red blood cell (RBC) transfusion after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with increased mortality but prior studies have not adequately adjusted for transfusion-indication bias. This is a retrospective study of consecutive aSAH patients admitted to the intensive care units of two academic medical centers over a 7-year period. Data collection included demographics, World Federation of Neurosurgical Surgeons score (WFNS), modified Fisher score (mFisher), admission and nadir hemoglobin (Hb) level, vasospasm, cerebral infarction, acute lung injury, and hospital mortality. The association between RBC transfusion and mortality was evaluated using a multivariate logistic regression analysis using the propensity for RBC transfusion as a covariate. We identified 318 patients. The median age was 54 years (46, 65), and 204 (64 %) were females. Hospital mortality was 13 % (42/318). Seventy-two (23 %) patients were transfused. Predictors of transfusion were admit and nadir Hb levels (p

Background Willis-Ekbom disease (WED), also called restless legs syndrome (RLS), is a neurologic sensorimotor disease that may be associated with cardiovascular disease. Given high morbidity and mortality rates of cardiovascular disease worldwide, we assessed the relation between WED/RLS and cardiovascular health risks in a native South American population. We prospectively analyzed data from The Atahualpa Project of Ecuadorian adults aged 40 years and older. Physicians interviewed consented persons on the health behavior and health factors of the American Heart Association (AHA) for ideal cardiovascular health in adults and underwent fasting laboratory blood collection and blood pressure evaluation. Certified neurologists conducted face-to-face interviews using the International Restless Legs Syndrome Study Group (IRLSSG) field instrument. Persons testing positive for WED/RLS and age-and sex-matched controls underwent confirmatory physical examinations conducted by a neurologist and a sleep specialist to whom IRLSSG designation was blinded. Findings Of 665 persons, 94 (14 %) tested positive in IRLSSG; 40 (6 %) had a diagnosis of WED/RLS after neurologic examination and interview. Patients with WED/RLS were younger (53.5 vs 59.9 years, P = .001), without significant differences in sex ratios. Among AHA risk factors, only obesity was significantly more prevalent among patients with WED/RLS (42.5 % vs 23.5 %, P = .01). However, after adjustment for confounders, body mass index was not significantly associated with WED/RLS. Conclusions In adult Amerindians, although obesity and body mass index were associated with WED/RLS on univariate analyses, the association was not present after adjustment for confounders. No other significant associations were found between WED/RLS and AHA cardiovascular metrics.

Correct diagnosis of diffuse cystic lung diseases is established in most cases by critical review of HRCT features http://ow.ly/NvrCc

Summary Serum and plasma are used interchangeably to measure anti-neutrophil cytoplasmic antibodies (ANCA), even though the release of ANCA target antigens during the preparation of serum could affect ANCA assays and cause discrepancies between the results obtained from serum and plasma. To what extent ANCA test results obtained from serum agree and correlate with results from plasma remains unknown. Therefore, a comprehensive comparison was performed using serum and plasma samples which were collected in 175 patients with active Wegener's granulomatosis at enrolment of a recent randomized trial. These paired serum and plasma samples were subjected to parallel ANCA testing by standard indirect immunofluoresence on ethanol-fixed neutrophils, a direct enzyme-linked immunoassay (ELISA) for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, and two different capture ELISAs for PR3-ANCA. The concordance of categorical serum and plasma ANCA results was assessed using κ-coefficients. These were > 0·8 for all assays, indicating a very good concordance between positive and negative serum and plasma results. Spearman's correlation coefficients for serum and plasma PR3-ANCA values obtained by direct ELISA and both capture ELISAs were ≥ 0·95 (P

(CHEST 2005; 127:1045–1050) A 70-year-old white man was referred for evaluation of pulmonary infiltrates and bronchiectases associated with cough and constitutional symptoms. He was in his usual state of health until he acquired B-cell non-Hodgkin lymphoma (NHL) in 1990. The lymphoma was localized to his stomach, and he was treated with surgical resection; chemotherapy with cyclophosphamide, vincristine, prednisone, and hydroxyurea; and radiation to the gastric bed. One year later, left lower lobe pneumonia developed that was treated with antibiotics. Because of persistent infiltrates, bronchoscopy was performed, with biopsy specimens revealing no abnormalities, and bronchiectases was diagnosed based on radiographic features. Three years prior to presentation, a cough productive of green-to-yellow sputum without hemoptysis developed. One year prior to presentation, progressive fatigue, anorexia, low-grade fevers, significant night sweats, and subsequent 20-lb weight loss developed. He denied other respiratory complaints. CT of the chest revealed patchy areas of consolidation in both lower lungs and in the right middle lobe along with mild mediastinal lymph node enlargement. Multiple sputum samples for acid-fast bacilli, bacteria, and fungi were negative. Endoscopic evaluations of his upper and lower intestinal tracts did not reveal recurrence of the lymphoma. Established medical problems included hypothyroidism and a previous myocardial infarction with subsequent revascularization surgery. He never smoked, and his family, social, and exposure history were otherwise noncontributory. He was referred to our tertiary care center for evaluation of productive cough, pulmonary infiltrates, worsening fatigue, persistent low-grade fevers with night sweats, and weight loss.

Hematopoietic stem cell transplantation (HSCT)has become the standard technique of bone marrowtransplantation (B M T ); nearly 20,000 procedureswere performed in North America during 1998 [1] .The donor source may be the patient (autologous), asibling or unrelated person (allogeneic), an identicaltwin (syngeneic), or a genetically-unrelated umbilicalcord blood sample [2] . Although syngeneic grafts donot develop graft-versus-host disease (GVHD) andhave low er treatm ent-related m ortality com paredwith allogeneic transplants, the advantages are oftencounterbalanced by a greater risk of malignant re-lapse. Thus, overall mortality is similar for syngeneicand allogeneic BMT .T he process of H S C T involves three stages:(1 ) conditioning of the recipien t, (2) inf usion ofhematopoietic stem cells, and (3) engraftment. Con-ditioning may involve cytoreductive therapy with orwithout total body irradiation (TBI). For solid tumors,high-dose cytoreductive chemotherapy may be usedin an attempt to achieve complete tumor ablation.Some chemoth erape utic age nts (eg, cyc lophosp ha-mide and busulfan) are direct pulmonary toxins thatcan lead to the development of drug-induced lunginjury and interstitial pneumonitis [3] . TBI also maybe used during the conditioning phase to prevent therelapse of the primary disease and graft failure. Dose-related, radiation-induced lung injury is reflected bya reduc tion in diffusing capac ity of the lung [4] .Furthermore, the combination of high-dose chemo-therapy and TBI synergistically increases the inci-dence and the severity of pulmonary complications[5] . In fact, idiopathic pneumonia syndrome (IPS)may be a direct consequence of radiation- and chemo-therapy-induced lung injury [6] .Th e hema topoi etic stem ce lls can be coll ect edfro m bon e marr ow , peri pher al blood , plac enta , orumbilical cord blood (T able 1) . Peripheral blood hasbecome the preferred source of stem cells for autolo-gous recipients because iteliminates the need for gen-eral anesthesia that is associated with bone marrowas piration. He m atopo ietic stem cells that are har-vested from the patientO s peripheral blood after treat-m ent with gra nul ocy te colo ny Ð stim ulat ing factor(G-CSF) or granulocyte-macrophage colony Ð stimu-lating factor (GM-CSF) are being used increasingly inautologous recipients. F or alloge ne ic H S CT , tech-niques, such as removal of T lymphocytes from thedonor graft, have lowered the incidence of GVHD.N onetheless, recipients are still prone to develop-ment of cytomegalovirus (CMV) infection, invasivefungal infections, and Epstein-Barr virus Ð associatedposttransplantation lymphoproliferative disease. Morerecently , hematopoietic stem cells from placental orumbilical cord blood were used to perform allogeneictransplants. This technique also is associated with alower incidence of graft rejection and GVHD [7] .Engraftment is defined as an absolute neutrophilcount that is greater than 0.5 ! 10

Objective Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL. Methods HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme-linked immunosorbent assays using purified native HNE as target antigen. Results Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven percent of HNE ANCA–positive CIMDL sera were also PR3 ANCA–positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA–negative, as were sera obtained from healthy controls. Conclusion Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.

To evaluate the utility of anti-nuclear antibody (ANA) levels in distinguishing the cause of pulmonary arterial hypertension as idiopathic (IPAH) or connective tissue disease related (CTD-PAH).We retrospectively identified patients with IPAH or CTD-PAH seen between 2010 and 2012 at our institution. Medical records were reviewed for demographic and clinical data and laboratory values.Of 115 patients identified, 65 (56%) had IPAH and 50 (44%) had CTD-PAH. The mean age was 59 years and most of the patients (76%) were women. Most patients (64%) were in World Health Organization functional class III or IV. Compared with the IPAH group, the CTD-PAH group had significantly increased B-type natriuretic peptide levels (635 vs 325 pg/mL; P = 0.02) and decreased pulmonary vascular resistance (6 vs 9 WU; P = 0.04). The median ANA level was significantly higher in the CTD-PAH group than the IPAH group (7 vs 0 U; P0.001). The area under the receiver operating characteristic curve for a positive ANA to predict CTD-PAH was 0.91 (P0.001). A cutoff of 5 U for predicting ANA provided an optimal specificity of 94% and a sensitivity of 70%. The resulting likelihood ratio using the same cutoff was 12 (P0.001), or a positive predictive value of 91% with a negative predictive value of 79%.In this selected cohort of patients, a quantitative ANA value5 U may be useful in distinguishing CTD-PAH from IPAH, but a lower level does not confidently exclude CTD-PAH.

Background Gastroesophageal reflux plays an important role in chronic cough (CC). Whether disturbed esophageal motility contributes to increased esophageal reflux exposure or interferes with swallowed bolus clearance is unclear. This study used high resolution esophageal manometry and impedance (HRIM) together with Chicago Classification, and 24-h impedance pH (MII/pH) to address these questions in patients with CC compared with heartburn (HB). Methods A retrospective review of 32 patients with CC (mean age 57 [95% CI: 52–62] years) and 32 patients with symptoms of HB (55 [52–62] years) referred for HRIM and MII/pH between September 2012 and September 2013 was undertaken. Key Results Weak peristalsis with large breaks (WPLBs) was observed in 34% of CC patients compared with only 12% of HB patients (p = 0.027). Pathological acid exposure time (AET) was identified in 81% of CC patients with WPLBs compared with 29% without (p = 0.011). Increased AET was associated with prolonged clearance time of refluxed events (p = 0.006) rather than increased number of events. AET correlated with the percentage of peristaltic events with large breaks in CC (ρ = 0.467, p = 0.007). Similar data were obtained for total bolus (acid and non-acid) exposure time. Only one of the CC patients with WPLBs exhibited complete bolus transit (CBT) on swallowing compared with 81% without WPLBs (p

Obstructive sleep apnea (OSA) may increase the risk of respiratory complications and acute respiratory distress syndrome (ARDS) among surgical patients. OSA is more prevalent among obese individuals; obesity can predispose to ARDS.It is unclear whether OSA independently contributes towards the risk of ARDS among hospitalized patients.This is a pre-planned retrospective subgroup analysis of the prospectively identified cohort of 5,584 patients across 22 hospitals with at least one risk factor for ARDS at the time of hospitalization from a trial by the US Critical Illness and Injury Trials Group designed to validate the Lung Injury Prediction Score. A total of 252 patients (4.5%) had a diagnosis of OSA at the time of hospitalization; of those, 66% were obese. Following multivariate adjustment in the logistic regression model, there was no significant relationship between OSA and development of ARDS (OR = 0.65, 95%CI = 0.32-1.22). However, body mass index (BMI) was associated with subsequent ARDS development (OR = 1.02, 95%CI = 1.00-1.04, p = 0.03). Neither OSA nor BMI affected mechanical ventilation requirement or mortality.Prior diagnosis of OSA did not independently affect development of ARDS among patients with at least one predisposing condition, nor the need for mechanical ventilation or hospital mortality. Obesity appeared to independently increase the risk of ARDS.

Global cerebral edema (GCE) with subsequent refractory intracranial hypertension complicates some cases of aneurysmal subarachnoid hemorrhage (aSAH), and typically is associated with poorer outcome. Treatment options for refractory intracranial pressure (ICP) cases are limited to decompressive hemicraniectomy (DHC) and targeted temperature management (TTM) with induced hypothermia (32-34 °C). No outcomes comparison between patients treated with either or both forms of refractory ICP therapy exists, and data on the effect of prolonged hypothermia on ICP and organ function among patients with aSAH are limited.This is a retrospective study of aSAH patients who underwent DHC and/or prolonged hypothermia (greater than 48 h) for refractory ICP (i.e., ICP20 mmHg after osmotherapy) in the intensive care unit of a single, tertiary-care academic center.Nineteen individuals with aSAH underwent TTM with or without DHC; sixteen patients underwent DHC alone. The patients in TTM group were younger (median age 44 years) than the DHC without TTM population (median age 60 years). TTM was started on median day 2 with a median duration of 7 days. There were no significant group differences in survival to discharge (59 % vs. 69 %) or in the mean modified Rankin score on follow-up (3.6 vs. 3.7), despite the TTM group having longer hospital length of stay (24 vs. 19 days, p = 0.03), longer duration of mechanical ventilation (20 vs. 9 days, p = 0.04), a higher cumulative fluid balance (12.8 vs. 5.1 L, p = 0.01), and higher APACHEII scores. The median maximal ICP decreased from 23.5 to 21 mmHg within 24 h of hypothermia initiation. There were no significant differences in other markers of end-organ function (respiratory, hematologic, renal, liver, and cardiac), infection rate, or adverse events between groups.Use of prolonged TTM among aSAH patients with GCE and refractory ICP elevations is associated with a longer duration of mechanical ventilation but is not different in terms of neurological outcomes measured by modified Rankin score or organ function outcomes compared to patients who received DHC alone.

Submaximal exercise testing (SET) assesses functional exercise capacity in pulmonary arterial hypertension (PAH) patients and provides additional physiologic information compared with the 6-min walk test (6MWT). The relative correlations of the 6MWT and SET using SHAPE-HF™ with other markers of PAH severity, particularly echocardiogram (ECHO)-derived mean pulmonary artery pressure (MPAP), have not been investigated.(i) Examine the correlation between SHAPE measures with the 6-min walk distance (6MWD), and (ii) Compare SHAPE parameters and the 6MWD to clinical measures of PAH severity.Fifty-five consecutive group 1 PAH outpatients were evaluated in a single pulmonary hypertension referral center from March 2011 to June 2012.World Health Organization (WHO) functional class (FC), brain natriuretic peptide (BNP), ECHO, 6MWD and SHAPE results. Data are reported using mean ± standard deviation and Spearman correlation coefficients (r).Nine patients were excluded. Of the 46 remaining patients, 78% were women and the average age was 61 ± 13 years. PAH characteristics: WHO FC III-IV 48%; idiopathic PAH 52%; BNP 198 ± 277 pg/mL; 6MWD 399 ± 97 m; ECHO right atrial pressure (RAP) 7 ± 4, pulmonary artery systolic pressure (PASP) 63 ± 29 and MPAP 45 ± 17 mmHg. SET with SHAPE results: mean partial pressure of end-tidal (PET ) CO2 31 ± 6 mmHg at end-exercise; ventilatory efficiency (VE/VCO2 ) 43 ± 16. Significant correlations were found between the 6MWD and SHAPE variables: VE/VCO2 (r = -0.57, P 0.0001) and end-exercise PET CO2 (r = 0.42, P = 0.004). VE/VCO2 correlated with WHO FC, BNP, RAP, MPAP and PASP and 6MWD only with WHO FC, BNP and PASP.SHAPE outperformed 6MWD in comparison with other measures of PAH disease severity.

Systemic air embolism is a very rare (

BACKGROUND: Nebulized drug delivery is a cornerstone of therapy for obstructive lung disease, but the ideal nebulizer design is uncertain. The breath-actuated nebulizer (BAN) may be superior to conventional nebulizers. This study compared the BAN to standard nebulizer with regard to efficacy, safety, and patient and respiratory therapist (RT) satisfaction. METHODS: Adults admitted to the hospital and for whom nebulizer therapy was prescribed were enrolled. Subjects were randomly assigned to either AeroEclipse II or standard nebulizer and were surveyed at the completion of each treatment. BAN delivered albuterol 2.5 mg or albuterol 2.5 mg plus ipratropium 0.25 mg. Standard nebulizer delivered albuterol 2.5 mg or albuterol plus ipratropium 0.5 mg. An RT assessed each subject's heart rate, respiratory rate, and peak expiratory flow rate prior to and following treatment. Treatment time and adverse events were recorded. Each RT was asked to assess his/her satisfaction with each of the nebulizers. RESULTS: Twenty-eight subjects were studied. The mean age was 69 years. Fifty-four percent of the subjects indicated that overall the BAN was superior to conventional nebulizer therapy; 68% indicated that duration was preferable with the BAN. RTs were more satisfied with the BAN, based on overall performance, treatment duration, and ease of use. There were no significant differences in heart rate, peak expiratory flow rate, or respiratory rate before or after nebulization therapy with either device. The duration of treatment was significantly lower with the BAN (4.1 min vs 9.9 min, P < .001). Additionally, the BAN was associated with a lower occurrence of adverse events. CONCLUSIONS: Patients and RTs expressed greater satisfaction with the BAN, compared with standard nebulizer. Pre- and post-treatment vital signs did not differ between groups, but use of the BAN was associated with a shorter duration and a lower occurrence of adverse events. Taken together, these data support the use of the BAN for nebulized medication delivery.

Amiodarone has been implicated as a risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) when used in the hospital. This study aims to estimate whether prehospital amiodarone also increases the risk of ALI/ARDS.Adult patients admitted to 22 centers with at least 1 risk factor for developing ALI were recruited. In a secondary analysis of this cohort, the prehospital use of amiodarone was documented on admission, and the patients followed for the primary outcome of ALI and secondary outcomes of ARDS, the need for invasive ventilation, and mortality. Dose/duration of amiodarone therapy was not available. Propensity matching was performed to account for imbalances in being assigned to amiodarone. The adjusted risk for ALI/ARDS was then estimated from a conditional logistic regression model of this propensity-matched set.Forty of 5584 patients were on amiodarone at the time of hospitalization; of those, 6 developed ALI, with 5 progressing to ARDS. In comparison, 371 patients not on amiodarone developed ALI, with 224 having ARDS. After propensity score matching, the prehospital use of amiodarone was not statistically associated with an increased risk for all ALI (odds ratio [OR], 1.8; 95% confidence interval [CI], 0.7-5.0; P = .25), invasive ventilation (OR, 1.9; 95% CI, 1.0-3.6; P = .059), or in-hospital mortality (OR, 1.2; 95% CI, 0.5-2.9; P = .75); but its use appeared to significantly increase the risk for ARDS (OR 3.8; 95% CI, 1.1-13.1; P = .036).Prehospital use of amiodarone may independently increase the risk for ARDS in patients who have at least 1 predisposing condition for ALI.

Pulmonary vasculitis can occur in apparent isolation, as part of a primary systemic vasculitis, or with an underlying systemic inflammatory autoimmune disorder. The presentation of pulmonary vasculitis in the intensive care unit (ICU) can be fulminant and will often overlap with more common disorders that affect the critically ill. Although diffuse alveolar hemorrhage (DAH) is the clinical feature that often initiates the concern for an underlying vasculitis, hemoptysis may not be apparent or its presentation can be mistaken for an alternative disease process. As a result, the diagnosis of pulmonary vasculitis in the ICU may be delayed or be completely unrecognized. A high level of suspicion is essential to obtain a timely diagnosis and for effective therapies to be implemented. There have been significant advances this past decade in diagnostic strategies as well as in the therapeutic options for patients with pulmonary vasculitis. We review here the clinical presentations, diagnostic strategies, and treatment options of the critically ill patients presenting with pulmonary vasculitis. The reader is referred to other resources for a more comprehensive review of specific vasculitic entities.

Testing for antineutrophil cytoplasmic antibodies (ANCA) reacting with proteinase 3 (PR3) is part of the routine diagnostic evaluation of patients with small vessel vasculitis. For PR3-ANCA detection, capture ELISAs are reported to be superior to direct ELISAs. Standard capture ELISAs, in which PR3 is anchored by anti-PR3 monoclonal antibodies (moAB), have two potential disadvantages. First, the capturing moAB may compete for epitopes recognized by some PR3-ANCA, causing occasional false-negative results. Second, the capture of recombinant PR3 mutant molecules becomes unpredictable as modifications of specific conformational epitopes may not only affect the binding of PR3-ANCA, but also the affinity of the capturing anti-PR3 moAB. Here, we describe a new capture ELISA, and its application for PR3-ANCA detection. This new assay is based on the standardized capture of a variety of different carboxy-terminally c-myc tagged recombinant ANCA target antigens using anti-c-myc coated ELISA plates. Antigen used include c-myc tagged human rPR3 variants (mature and pro-form conformations), mouse mature rPR3 and human recombinant neutrophil elastase. This new anti-c-myc-capture ELISA for PR3-ANCA detection has an intra- and inter-assay coefficient of variation of 3.6% to 7.7%, and 15.8% to 18.4%, respectively. The analytical sensitivity and specificity for PR3-ANCA positive serum samples were 93% and 100%, respectively when rPR3 with mature conformation was used as target antigen, and 83% and 100% when the pro-enzyme conformation was employed. In conclusion, this new anti-c-myc capture ELISA compares favorably to our standard capture ELISA for PR3-ANCA detection, enables the unified capture of different ANCA target antigens through binding to a c-myc tag, and allows capture of rPR3 mutants necessary for PR3-ANCA epitope mapping studies.