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CHEST publishes select peer-reviewed, accepted manuscripts Online First each week. The media embargo is lifted on the date of Online First publication. Final, edited versions will appear in a numbered issue of CHEST and may contain substantive changes. We encourage readers to check back for the final article. Online First papers are indexed in PubMed and by search engines, but the information, including the final title and author list, may be updated on final publication.

original research 
P.P. Walker; E. Thwaite; S. Amin; J. Curtis; P.M.A. Calverley
Topics: , , ,

Background:  Inhalation/smoking has become the most common method of recreational opiate consumption in the UK and other countries. Although some heroin smokers appear to develop COPD little is known about the association.

Methods:  We present data from a cohort of 73 heroin smokers with clinician diagnosed and spirometrically confirmed COPD, seen within our clinical service, where symptoms developed before the age of 40 years.

Results:  The whole group mean age at diagnosis was 41 years, subjects had smoked heroin for 14 years and mean FEV1 was 1.08L (31.5% predicted) with mean FEV1/FVC of 0.4. No subject was found to have severe alpha-1-anti-trypsin deficiency. Forty four subjects had either a high-resolution CT scan (32) or measurement of lung diffusion (12). Overall HRCT emphysema score averaged across the upper, middle and lower part of the lung was 2.3 (5-25% emphysema) with 47% subjects having an upper lobe emphysema score of 3 or greater (25-50% emphysema). Median DLCO was 48% of predicted value.

Conclusions:  Recreational smoking of heroin appears to lead to early onset COPD with a predominant emphysema phenotype. This message is important both to clinicians and the public and targeted screening and education of this high risk population may be justified.

original research 
Marwan M. Azar, MD; Roland Assi, MD, MS; Ryan F. Relich, PhD, MLS(ASCP)CM; Bryan H. Schmitt, DO; Steven Norris, MD; L. Joseph Wheat, MD; Chadi A. Hage, MD, FCCP

Background:  To better understand clinical and epidemiologic patterns of blastomycosis, we report on a large series of blastomycosis in Indiana.

Methods:  All microbiologically and histopathologically-confirmed cases of blastomycosis from four hospitals serving central Indiana from 1985 to 2014 were identified. Available data were collected. Data on population estimates, annual precipitation and construction in Indiana were evaluated for correlations with incidence rates of blastomycosis.

Results:  A total of 114 patients were identified. The mean age was 44.4; 27% had diabetes mellitus (DM) and 16% were immunosuppressed. Most presented with pneumonia (90%); 48% had extrapulmonary disease (central nervous system involvement in 9%) and 15% developed Acute Respiratory Distress Syndrome. Cultures, cytopathology and histopathology were positive in 86%, 27%, and 85% of the sample respectively while fungal antigen was positive in 76%. Amphotericin B was administered in 49% and 87% received an azole. Total mortality was 12%. Immunosuppression (OR=3.0), DM (OR=2.9), and multilobar pneumonia (OR=2.9) were associated with increased likelihood of ICU admission. There was a significant increase in incidence over time in Marion County. There was no correlation with amount of precipitation but the rise in incidence coincided with a 2005 state initiative to expand Indiana's highway infrastructure.

Conclusion:  The incidence of blastomycosis in central Indiana may be on the rise. Physicians in endemic areas should be aware of the potentially fulminant consequences of the disease.

original research 
Matthew R. Lammi, MD; Brianne Aiello, MD; Gregory T. Burg, MD; Tayyab Rehman, MD; Ivor S. Douglas, MD; Arthur P. Wheeler, MD; Bennett P. deBoisblanc, MD; For the NIH NHLBI ARDS Network Investigators

Background:  Recent emphasis has been placed on methods to predict fluid-responsiveness (FR), but the utility of using fluid boluses to increase cardiac index (CI) in critically-ill patients with ineffective circulation or oliguria remains unclear.

Methods:  Retrospective analysis investigating hemodynamic responses of critically ill patients in the ARDS Network Fluid and Catheter Treatment Trial (FACTT) who were given protocol-based fluid boluses. FR was defined as ≥15% increase in CI after a 15ml/kg fluid bolus.

Results:  A convenience sample of 127 critically-ill patients enrolled in FACTT was analyzed for physiologic responses to 569 protocolized crystalloid or albumin boluses given for shock, low urine output (UOP), or low pulmonary artery occlusion pressure (PAOP). There were significant increases in mean central venous pressure (9.9±4.5 to 11.1±4.8 mmHg, p<0.0001) and mean PAOP (11.6±3.6 to 13.3±4.3 mmHg, p<0.0001) following fluid boluses. However, there were no significant change in UOP, and clinically small changes in heart rate (HR), mean arterial pressure (MAP), and CI. Only 23% of fluid boluses led to a ≥15% change in CI. There was no significant difference in the frequency of fluid responsiveness between boluses given for shock or oliguria versus boluses given only for low PAOP (24.0% vs. 21.8%, p=0.59). There were no significant differences in 90-day survival, need for hemodialysis, or return to unassisted breathing between patients defined as fluid responders and fluid non-responders.

Conclusion:  In this cohort of critically-ill and previously resuscitated ARDS patients, the rate of fluid responsiveness was low and fluid boluses only led to small hemodynamic changes.

point and counterpoint 
Kenneth I. Berger, M.D.; Roberta M. Goldring, M.D.; Beno W. Oppenheimer, M.D.
Topics: , ,

Detection of airway disease by physiologic testing was initially described using spirometry to determine vital capacity and expiratory airflow under maximal effort to distinguish obstructive from restrictive disease processes. Subsequently, Dubois demonstrated direct assessment of airway resistance using plethysmography and in a separate publication described the precursor of the forced oscillation technique to measure respiratory system resistance. This review addresses the question of whether direct assessment of resistance by forced oscillation provides diagnostic information equivalent or superior to standard assessment of airflow rates by spirometry.

point and counterpoint 
Paul L. Enright, MD
Topics: , ,

Pulmonary physiologists at the Mayo Clinic used a large loudspeaker to measure respiratory system resistance (Rrs) the year I was born (Figure 1). My first research project used a forced oscillator to measure bronchodilation during exercise in children with asthma. Joe Rodarte, from whom I learned pulmonary physiology at the Mayo Clinic said about the technique in 1990 that "one man's noise is another man's signal." After five generations and 65 years of improvements in forced oscillation technique (FOT) instrumentation and software, I remain cautiously optimistic that this test will eventually find clinical value.

point and counterpoint 
Kenneth I. Berger, M.D.; Roberta M. Goldring, M.D.; Beno W. Oppenheimer, M.D.
Topics: ,

We agree that the “holy grail” of pulmonary physiologists is a test that detects early chronic airway disease. While Dr. Enright remains “cautiously optimistic” that FOT can serve this purpose, there are sufficient data to mitigate his caution.

point and counterpoint 
Paul L. Enright, MD
Topics: , , ,

Several years ago, while working with Doctors Berger, Goldring, and Oppenheimer evaluating people who were exposed to World Trade Center (WTC) dust and fumes, I found them to be excellent pulmonary physiologists and I appreciate the high quality of their research using pulmonary function tests such as oscillometry (a FOT).

contemporary reviews in critical care medicine 
Kalpalatha K. Guntupalli, MD, FCCM, FCCP, MACP; Nicole Hall, MD; Dilip R. Karnad, MD, FACP, FRCP(Glasg); Venkata Bandi, MD, FCCP; Michael Belfort, MBBCH, MD, PhD, FRCOG
Topics: , , ,

Managing critically ill obstetric patients in the intensive care unit is a challenge because of their altered physiology, different normal ranges for laboratory and clinical parameters in pregnancy, and potentially harmful effects of drugs and interventions on the fetus. About 200 to 700 women per 100,000 deliveries require ICU admission. A systematic five-step approach is recommended to enhance maternal and fetal outcomes: (1) Differentiate between medical and obstetric disorders with similar manifestations, (2) identify and treat organ dysfunction, (3) assess maternal and fetal risk from continuing pregnancy and decide if delivery/termination of pregnancy will improve outcome, (4) choose an appropriate mode of delivery if necessary, and (5) optimize organ functions for safe delivery. A multidisciplinary team including the intensivist, obstetrician, maternal-fetal medicine specialist, anesthesiologist, neonatologist, nursing specialist and transfusion medicine expert is key to optimize outcomes. Severe preeclampsia and its complications, HELLP syndrome and amniotic fluid embolism, which cause significant organ failure, are reviewed. Obstetric conditions that were not so common in the past are increasingly seen in the ICU. Thrombotic thrombocytopenic purpura of pregnancy is being diagnosed more frequently. Massive hemorrhage from adherent placenta is increasing due to large number of pregnant women with scars from previous cesarean section. With more complex fetal surgical interventions being performed for congenital disorders, maternal complications are increasing. Ovarian hyperstimulation syndrome is also becoming common due to treatment of infertility with assisted reproduction techniques. Part II, will deal with common medical disorders and their management in critically ill pregnant women.

contemporary reviews in critical care medicine 
Kalpalatha K. Guntupalli, MD, FCCM, FCCP, MACP; Dilip R. Karnad, MD, FACP, FRCP(Glasg); Venkata Bandi, MD, FCCP; Nicole Hall, MD; Michael Belfort, MBBCH, MD, PhD, FRCOG
Topics: , ,

The first of this two part series on critical illness in pregnancy dealt with obstetric disorders. In Part II, medical conditions that commonly affect pregnant women or worsen during pregnancy are discussed. ARDS occurs more frequently in pregnancy. Strategies commonly used in non-pregnant patients including permissive hypercapnia, limits for plateau pressure, prone positioning may not be acceptable especially in late pregnancy. Genital tract infections unique to pregnancy include chorioamionitis, Group A streptococcal infection causing toxic shock syndrome, and polymicrobial infection with streptococci, staphylococci and clostridium perfringes causing necrotizing vulvitis or fasciitis. Pregnancy predisposes to venous thromboembolism; D-dimer levels have low specificity in pregnancy. A ventilation-perfusion scan is preferred over CT pulmonary angiography in some situations to reduce radiation to the mother’s breasts. Low-molecular weight or unfractionated heparins form the mainstay of treatment; vitamin K antagonists, oral Factor Xa inhibitors and direct thrombin inhibitors are not recommended in pregnancy. The physiological hyperdynamic circulation in pregnancy worsens many cardiovascular disorders. It increases risk of pulmonary edema or arrhythmias in mitral stenosis, heart failure in pulmonary hypertension or aortic stenosis, aortic dissection in Marfan’s syndrome, or valve thrombosis in mechanical heart valves. Common neurological problems in pregnancy include seizures, altered mental status, visual symptoms and strokes. Other common conditions discussed are aspiration of gastric contents, obstructive sleep apnea, thyroid disorders, diabetic ketoacidosis and cardiopulmonary arrest in pregnancy. Studies confined to pregnant women are available for only a few of these conditions. We have therefore reviewed pregnancy-specific adjustments in the management of these disorders.

special features 
Thomas O’Riordan, MD; Victoria Smith, PhD; Ganesh Raghu, MD

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fatal disease. Until recently, the standard therapy for this disease has been essentially supportive, with the exception of a minority of patients who were eligible for lung transplantation. The development pathway for novel medications for IPF has been complicated. There have been several challenges including an incomplete understanding of the pathogenesis, unpredictable clinical course, lack of validated biomarkers, the low clinical predictive value of animal models of lung injury, and the need to commit to large clinical trials of long duration to obtain initial evidence of clinical efficacy. Despite these challenges, the combination of recent advances in translational medicine and the unprecedented increase in clinical data accumulated from recent large clinical trials have served to stimulate an increase in the number of clinical development programs for IPF. Clinical programs are increasingly characterized by rational target selection, preclinical optimization of therapeutic molecules and an emphasis on efficient clinical trial design. A lower rate of functional decline in patients treated with pirfenidone and nintedanib was recently demonstrated in large clinical trials. In October 2014, these two drugs became the first agents to be approved by the US Food and Drug Administration (US FDA) for the treatment of IPF. (Pirfenidone had already been approved in several other countries outside the US). In Nov 2014, the European Medicines Agency (EMEA) approved the use of nintedanib for IPF. The landscape for management of IPF has markedly changed with the advent of approved therapeutic options for IPF. In this perspective, we review the strategies that are being employed to increase the likelihood of success in clinical development programs of novel disease modifying agents in IPF.

commentary 
David Gozal, MD, FCCP; Ramon Farré, PhD; F. Javier Nieto, PhD
Topics: , ,

In recent years, the potentially adverse role of sleep-disordered breathing in cancer incidence and outcomes has emerged. In parallel, animal models of intermittent hypoxia (IH) and sleep fragmentation (SF) emulating the 2 major components of obstructive sleep apnea (OSA) have lent support to the notion that OSA may enhance the proliferative and invasive properties of solid tumors. Based on several lines of evidence, we propose that OSA-induced increases in sympathetic outflow and alterations in immune function are critically involved in modifying oncological processes including angiogenesis. In this context, we suggest that OSA, via IH (and potentially SF), promotes changes in several signaling pathways and transcription factors that coordinate malignant transformation and expansion, disrupts host immunological surveillance, and consequently leads to increased probability of oncogenesis, accelerated tumor proliferation and invasion, ultimately resulting in adverse outcomes.

original research 
Felipe Cortopassi, PT, RPFT; Bartolome Celli, MD; Miguel Divo, MD; Victor Pinto-Plata, MD
Topics: , , ,

Introduction:  In chronic obstructive pulmonary disease (COPD), a decreased inspiratory/total lung capacity ratio (IC/TLC), is associated with dynamic hyperinflation (DH) and poor exercise capacity. The association to upper extremity force measured by handgrip strength (HGS) and 6 minute walk distance has not been described. We hypothesized that IC/TLC affects muscle strength of upper and lower extremities affecting HGS and the six minute walk test (6MWD) performance.

Methods:  We prospectively measured lung function, HGS and 6MWD in 27 patients with COPD and 12 healthy nonsmoking individuals twice, 1 year apart. The patients were classified according to level of hyperinflation in 2 groups, IC/TLC > or ≤ 25%.

Results:  Patients with COPD had reduced lung function, static hyperinflation, reduced HGS and 6MWD compared to the controls on both evaluations (p < 0.01). There was a statistically significant deterioration in HGS, IC/TLC and 6MWD after 1 year follow up in the COPD compared to the control group (p < 0.001). More hyperinflation (IC/TLC < .25) was associated with lower HGS and 6MWD (p < 0.001). Changes in IC/TLC correlated with changes in HGS (r = 0.429, p < 0.05). A multivariate analysis determined that IC/TLC was an independent factor associated to HSG and to 6MWD.

Conclusion:  Handgrip strength and 6MWD are reduced in patients with COPD, particularly in patients with hyperinflation with evidence of longitudinal deterioration not seen in controls. This suggests that resting hyperinflation may exert a detrimental effect on cardiac function and play a role in the reduced exercise performance in COPD patients.

original research 
Guillaume Dumas, MD; Guillaume Géri, MD; Claire Montlahuc, MD; Sarah Chemam, MD; Laurence Dangers, MD; Claire Pichereau, MD; Nicolas Brechot, MD; Matthieu Duprey, MD; Julien Mayaux, MD; Maleka Schenck, MD; Julie Boisramé-Helms, MD, PhD; Guillemette Thomas, MD; Loredana Baboi, PhD; Luc Mouthon, MD, PhD; Zair Amoura, MD, PhD; Thomas Papo, MD, PhD; Alfred Mahr, MD, PhD; Sylvie Chevret, MD, PhD; Jean-Daniel Chiche, MD, PhD; Elie Azoulay, MD, PhD
Topics: ,

Background:  Systemic rheumatic diseases (SRD) patients may require ICU management for SRD exacerbation, treatment-related infectious or toxicities.

Methods:  Observational study in 10 university-affiliated ICUs in France. Consecutive patients with SRD were included. Determinants of ICU mortality were identified through multivariable logistic analysis.

Results:  363 patients (65.3 % women, median age 59y (IQR, 42-70)) accounted for 381 admissions. Connective tissue disease (primarily Systemic Lupus Erythematosus) accounted for 66.1% of SRD and systemic vasculitides for 26.2 % (chiefly ANCA-associated vasculitides). SRD was newly diagnosed in 43 (11.3%) cases. Direct admission to ICU occurred in 143 (37.9%) cases. Reasons for ICU admissions were infection (39.9%), SRD exacerbation (34.4%), toxicity (5.8 %) or miscellaneous (19.9%). Respiratory involvement was the leading cause of admission (56.8 %), followed by shock (41.5 %) and acute kidney injury (42.2%). Median SOFA on day-1 was 5 [3-8]. Mechanical ventilation was required in 57% cases, vasopressors in 33.9% and renal replacement therapy in 28.1%. ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality were shock (OR: 3.77 [95%CI, 1.93 -7.36]), SOFA score at day 1 (OR: 1.19 [95%CI, 1.10-1.30]) and direct admission (OR: 0.52, [CI 0.28-0.97]. Neither comorbidities nor SRD characteristics were associated with survival.

Conclusions:  In SRD patients, critical care management is mostly needed in patients with previously known SRD; still, diagnosis can be made in the ICU in 12% of the patients. Infection and SRD exacerbation account for more than two-third of the situations, both targeting chiefly the lungs. Direct admission to the ICU might improve outcomes.

original research 
Roop Kaw, MD; Priyanka Bhateja, MD; Hugo Paz y Mar, MD; Adrian V. Hernandez, MD, PhD; Anuradha Ramaswamy, MD; Abhishek Deshpande, MD, PhD; Loutfi S. Aboussouan, MD
Topics: , , , ,

Background:  Among patients with obstructive sleep apnea (OSA) a higher number of medical morbidities are known to be associated with those that have obesity hypoventilation syndrome (OHS) compared to OSA alone. OHS can therefore pose a higher risk of postoperative complications after elective non-cardiac surgery (NCS) and is often unrecognized at the time of surgery. The objective of this study was to retrospectively identify patients with OHS and compare their postoperative outcomes with those who have OSA alone.

Methods:  Patients meeting criteria for OHS were identified within a large cohort of patients with OSA who underwent elective NCS at a major tertiary care center. We identified postoperative outcomes associated with OSA and OHS as well as the clinical determinants of OHS (BMI, AHI). Multivariable logistic or linear regression models were used for dichotomous or continuous outcomes, respectively.

Results:  Patients with hypercapnia from definite or possible OHS, and overlap syndrome are more likely to develop postoperative respiratory failure [OR: 10.9 (95% CI 3.7-32.3), p<0.0001], postoperative heart failure (p<0.0001), prolonged intubation [OR: 5.4 (95% CI 1.9-15.7), p=0.002), postoperative ICU transfer (OR: 3.8 (95% CI 1.7-8.6), p=0.002]; longer ICU (beta coefficient: 0.86; SE: 0.32, p=0.009) and hospital length of stay (beta coefficient: 2.94; SE: 0.87, p=0.0008) when compared to patients with OSA. Among the clinical determinants of OHS, neither BMI nor AHI showed associations with any postoperative outcomes in univariable or multivariable regression.

Conclusions:  Better emphasis is needed on preoperative recognition of hypercapnia among patients with OSA or overlap syndrome undergoing elective NCS.

original research 
Christopher J. Ryerson; Darragh O’Connor; James V. Dunne; Fran Schooley; Cameron J. Hague; Darra Murphy; Jonathon Leipsic; Pearce G. Wilcox
Topics: , , ,

Background:  Mortality risk prediction tools have been developed in idiopathic pulmonary fibrosis, however it is unknown whether these models accurately estimate mortality in systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Methods:  Four baseline risk prediction models were calculated in patients recruited from a specialized SSc-ILD clinic, including the Composite Physiologic Index (CPI), the ILD-GAP Index, the du Bois index, and the modified du Bois index. Each baseline model was assessed using logistic regression analysis with 1-year mortality as the outcome variable. Discrimination was quantified using the area under the receiver operating characteristic (AUROC) curve. Calibration was assessed using the goodness of fit test. The incremental prognostic ability of additional predictor variables was determined by adding prespecified variables to each baseline model.

Results:  The 156 patients with SSc-ILD completed 1294 pulmonary function tests, 725 6-minute walk tests, and 637 echocardiograms. Median survival was 15.0 years from the time of SSc-ILD diagnosis. All baseline models were significant predictors of 1-year mortality in SSc-ILD. The modified du Bois index had an AUROC curve of 0.84, compared to 0.77 to 0.81 in the other models. Calibration was acceptable for the modified du Bois index, but was poor for the other models. All baseline models include forced vital capacity, and 6-minute walk distance was identified as an additional independent predictor of 1-year mortality.

Conclusion:  The modified du Bois index has good discrimination and calibration for the prediction of 1-year mortality in SSc-ILD. FVC and 6-minute walk distance are important independent predictors of 1-year mortality in SSc-ILD.

original research 
David J. Blackley, DrPH; A. Scott Laney, PhD; Cara N. Halldin, PhD; Robert A. Cohen, MD
Topics: , , ,

Background  A large body of evidence demonstrates dose-response relationships of cumulative coal mine dust exposure with lung function impairment and with small opacity profusion. However, medical literature generally holds that simple coal workers’ pneumoconiosis (CWP) is not associated with lung function impairment. This study examines the relationship between small opacity profusion and lung function in U.S. underground coal miners with simple CWP.

Methods  Miners were examined during 2005–2013 as part of the Enhanced Coal Workers’ Health Surveillance Program. Work histories were obtained, and chest radiographs and spirometry were administered. For those with multiple Program encounters, the most recent visit was used. Lung parenchymal abnormalities consistent with CWP were classified according to International Labour Organization guidelines, and reference values for FEV1 and FVC were calculated using reference equations derived from the 3rd National Health and Nutrition Examination Survey. Differences in lung function were evaluated by opacity profusion, and regression models were fit to characterize associations between profusion and lung function.

Results  A total of 8,230 miners were eligible for analysis; 269 had category 1 or 2 simple CWP. Decrements in FEV1 percent predicted were nearly consistent across profusion subcategories. Clear decrements in FVC percent predicted and FEV1/FVC were also observed, although these were less consistent. Controlling for smoking status, BMI, and mining tenure, each one-unit subcategory increase in profusion was associated with decreases of 1.5% (95% CI 1.0% to 1.9%), 1.0% (95% CI 0.6% to 1.3%), and 0.6% (95% CI 0.4% to 0.8%) in FEV1 percent predicted, FVC percent predicted, and FEV1/FVC, respectively.

Conclusions  We observed progressively lower lung function across the range of small opacity profusion. These findings address a longstanding question in occupational medicine, and point to the importance of medical surveillance and respiratory disease prevention in this workforce.

original research 
Robert H. Brown, MD; Robert A. Wise, MD; Gregory Kirk, MD; M. Bradley Drummond, MD; Wayne Mitzner, PhD
Topics: ,

Background:  With body growth from childhood, the lungs can enlarge by either increasing the volume of air in the periphery (as would occur with inspiration) or by increasing the number of peripheral acinar units. In the former case the lung tissue density would decrease with inflation, while in the latter case, the lung density would be relatively constant as the lung grows. To address this fundamental structural question, we measured the CT density in human subjects of widely varying size at two different lung volumes.

Methods:  Five-hundred and one subjects were enrolled in the study. They underwent a chest CT at full inspiration, and another scan at end-expiration. Spirometry, body-plethysmography, and DLco were also measured.

Results:  There was a strong correlation between the size of the lungs measured at full inspiration on CT and the mean lung density (r=-.72, p=0.001). People with larger lungs had significantly lower mean lung density. These density changes among different subjects overlapped the density changes within subjects at different lung volumes.

Conclusion:  Lung structure in subjects with larger lungs is different from that in subjects with smaller lungs. Tissue volume does not increase in proportion to lung size, as would be required if bigger lungs just had more alveoli. These observations suggest that growth of the lung into adulthood is not accompanied by new alveoli, but rather by enlargement of existing structures. The presence of bigger air spaces in larger lungs could impact the occurrence and pathogenesis of spontaneous pneumothorax or COPD.

original research 
Matthew A. Rank, MD; Ryan Johnson, MBA, MS; Megan Branda, MS; Jeph Herrin, PhD; Holly van Houten; Michael R. Gionfriddo, PharmD; Nilay D. Shah, PhD

Background:  Long term outcomes after stepping down asthma medications are not well described.

Methods:  This study was a retrospective time-to-event analysis of individuals diagnosed with asthma who stepped down their asthma controller medications using a US claims database spanning 2000-2012. Four-month intervals were established and a step down event was defined by a ≥50% decrease in days-supplied of controller medications from one interval to the next; this definition is inclusive of step down that occurred without healthcare provider guidance or as a consequence of a medication adherence lapse. Asthma stability in the period prior to step down was defined by not having an asthma exacerbation (inpatient visit, emergency department visit, or dispensing of a systemic corticosteroid linked to an asthma visit) and having < 2 rescue inhaler claims in a 4-month period. The primary outcome in the period following step down was time to first asthma exacerbation.

Results:  Thirty-two percent of the 26,292 included individuals had an asthma exacerbation in the 24-month period following step down of asthma controller medication, though only 7% had an emergency department visit or hospitalization for asthma. The length of asthma stability prior to stepping down asthma medication was strongly associated with the risk of an asthma exacerbation in the subsequent 24-month period: < 4 months stability -44%, 4-7 months-34%, 8-11 months-30%, and ≥ 12 months-21%, p<.001.

Conclusion:  In a large, claims-based, real-world study setting, 32% of individuals have an asthma exacerbation in the 2 years following a step down event.

original research 
Hiroshi Sekiguchi, MD; Louis A. Schenck; Ryohei Horie, MD; Jun Suzuki, MD; Edwin H. Lee, MD; Brendan P. McMenomy, MD; Tien-En Chen, MD; Alexander Lekah, MD; Sunil V. Mankad, MD; Ognjen Gajic, MD
Topics: , , , ,

Background:  Pathogenic causes of acute hypoxic respiratory failure (AHRF) can be difficult to identify at early clinical presentation. We evaluated the diagnostic utility of combined cardiac and thoracic critical care ultrasonography (CCUS).

Methods:  Adult patients in the intensive care unit (ICU) were prospectively enrolled from January through September 2010 when the ratio of Pao2 to fraction of inspired oxygen (Fio2) was less than 300 on arterial blood gas (ABG) within 6 hours of a new hypoxic event or ICU admission. Focused cardiac and thoracic CCUS was conducted within 6 hours of ABG testing. Causes of AHRF were categorized into cardiogenic pulmonary edema (CPE), acute respiratory distress syndrome (ARDS), and other, miscellaneous causes after reviewing the hospitalization course in electronic medical records.

Results:  Enrollment involved 134 patients (median [interquartile range] Pao2/Fio2 ratio, 191 [122-253]). Fifty-nine patients (44%) received a CPE diagnosis; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis on CCUS findings showed that a low B-line ratio (proportion of chest zones with positive B-lines of all zones examined) was predictive for miscellaneous cause vs CPE or ARDS. Area under the receiver operator characteristic curve (AUC) was 0.82 (95% CI, 0.75-0.88). For further differentiation of CPE from ARDS, left pleural effusion (>20 mm), moderately or severely decreased left ventricular function, and a large minimal inferior vena cava diameter (>23 mm) were predictive for CPE. AUC was 0.79 (95% CI, 0.70-0.87).

Conclusions:  Combined cardiac and thoracic CCUS assists in early bedside differential diagnosis of ARDS, CPE, and other causes of AHRF.

ahead of the curve  FREE TO VIEW
Jason R. Biehl, MD; Ellen L. Burnham, MD, MSc
Topics: , ,

Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety among the medical and scientific community. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly since published data conducted prior to widespread legalization are conflicting and inconclusive. In this Ahead of the Curve, we delineate major observations of recent epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we will review major histopathologic alterations related to smoked cannabis, and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given its ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain, and given increasing use patterns, worthy of further investigation.

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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543