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original research 
Deena Kelly Costa, PhD, RN; Matthew White; Emily Ginier, MLIS; Milisa Manojlovich, PhD, RN, CCRN; Sushant Govindan, MD; Theodore J. Iwashyna, MD, PhD; Anne E. Sales, PhD, RN

Background  Improved outcomes are associated with the Awakening, Breathing Coordination, Delirium and Early mobility/exercise (ABCDE) bundle; however, implementation issues are common. As yet, no study has integrated the barriers to ABCDE to provide an overview of reasons for less successful efforts. The purpose of this review was to identify and catalog the barriers to ABCDE delivery based on a widely used implementation framework, and provide a resource to guide clinicians in overcoming barriers to implementation.

Methods  We searched MEDLINE via PubMed, CINAHL, and Scopus for original research from January 1, 2007 to August 31, 2016 that identified barriers to ABCDE implementation for adult intensive care unit (ICU) patients. Two reviewers independently reviewed studies, extracted barriers and conducted thematic content analysis of the barriers, guided by the Consolidated Framework for Implementation Research. Discrepancies were discussed and consensus achieved.

Results  Our electronic search yielded 1908 articles. After applying our inclusion/exclusion criteria, we included 49 studies. We conducted thematic content analysis of the 107 barriers and identified 4 classes of ABCDE barriers: 1) patient-related (i.e. patient instability and safety concerns); 2) clinician-related (i.e. lack of knowledge, staff safety concerns); 3) protocol-related (i.e. unclear protocol criteria, cumbersome protocols to use); and—not previously identified in past reviews—4) ICU contextual barriers (i.e. interprofessional team care coordination).

Conclusions  We provide the first systematic differential diagnosis of barriers to ABCDE delivery, moving beyond the conventional focus on patient-level factors. Our analysis offers a differential diagnosis checklist for clinicians planning ABCDE implementation to improve patient care and outcomes.

contemporary reviews in critical care medicine  OPEN ACCESS
Elie Azoulay, MD, PhD; Paul Knoebl, MD; José Garnacho-Montero, MD, PhD; Katerina Rusinova, MD, PhD; Gennadii Galstian, MD, PhD; Philippe Eggimann, MD, PhD; Fekri Abroug, MD, PhD; Dominique Benoit, MD, PhD; Michael von Bergwelt-Baildon, MD, PhD; Julia Wendon, MD; Marie Scully, MD
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Background  Atypical haemolytic uraemic syndrome (aHUS) presents similarly to thrombotic thrombocytopenic purpura (TTP), and other causes or conditions with thrombotic microangiopathy (TMA) such as DIC or sepsis. Similarity in clinical presentation may hinder diagnosis and optimal treatment selection in the urgent setting in the ICU. However, there is currently no consensus on the diagnosis or treatment of aHUS for ICU specialists. This review aims to summarise available data on the diagnosis and treatment strategies of aHUS in the ICU in order to enhance the understanding of aHUS diagnosis and outcomes in patients managed in the ICU.

Methods  A review of the recent literature (January 2009 – March 2016) was performed to select the most relevant articles for ICU physicians.

Results  Based on the paucity of adult aHUS cases overall and within the ICU, no specific recommendations could be formally graded for the critical care setting. However, the expert panel recognises a core set of skills required by intensivists for diagnosing and managing patients with aHUS: recognising thrombotic microangiopathies, differentiating aHUS from related conditions, recognising involvement of other organ systems, understanding the pathophysiology of aHUS, knowing the diagnostic workup and relevant outcomes in critically ill aHUS patients, and knowing the standard of care for patients with aHUS based on available data and guidelines.

Conclusions  Managing critically ill patients with aHUS requires basic skills that, in the absence of sufficient data from patients treated within the ICU, can be gleaned from an increasingly relevant literature outside the ICU. More data on critically ill patients with aHUS are needed to validate these conclusions within the ICU setting.

ahead of the curve 
Eva Polverino, MD, PhD; Edmundo Rosales-Mayor, MD; Glenn E. Dale, PhD; Klaus Dembowsky, MD, PhD; Antoni Torres, MD, PhD, Prof.
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In many respiratory diseases characterised by an intense inflammatory response, the balance between proteolytic enzymes (proteases, including elastases) and their inhibitors (proteinases inhibitors) is not neutral. In fact, an excess activity of neutrophil elastase (NE) and similar proteases has been reported to cause tissue damage and to alter the remodelling process in many clinical conditions such as pneumonia, respiratory distress and acute lung injury [ALI]. In recent years, several experimental NE inhibitors have been tested in preclinical and clinical studies of different conditions of inflammatory lung injury such as ALI and pneumonia, with contrasting results. This study reviews the literature regarding NE inhibitors in the field of respiratory diseases and reflects on possible future developments. In particular, we highlight potential gaps in the current scientific evidence and discuss potential strategies for focusing investigation on anti-elastases in clinical practice through the selection of targeted populations and proper outcomes.

original research 
Judy L. Jensen, MS; Christopher R. Jones, MD, PhD; Christiana Kartsonaki, DPhil; Kristyn A. Packer, MA; Frederick R. Adler, PhD; Theodore G. Liou, MD
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Background  Cystic fibrosis (CF) transmembrane regulator (CFTR) protein dysfunction causes CF. Improving survival allows detection of increasingly subtle disease manifestations. CFTR dysfunction in the central nervous system (CNS) may disturb circadian rhythm and thus sleep phase. We studied sleep in adults to better understand potential CNS CFTR dysfunction.

Methods  We recruited participants from April 2012 through April 2015 and administered the Munich Chronotype Questionnaire (MCTQ). We compared free-day sleep measurements between CF and non-CF participants and investigated associations with CF survival predictors.

Results  We recruited 23 female and 22 male adults with CF aged 18-46 years and 26 female and 22 male volunteers aged 18-45 years. Compared to non-CF volunteers, patients with CF had delayed sleep-onset (0.612 hrs, P = 0.015), mid-sleep (1.11 hrs, P < 0.001) and wake-up (1.15 hrs, P < 0.001) times and prolonged sleep latency (7.21 min, P = 0.05) and duration (0.489 hr, P = 0.05). Every hour delay in sleep-onset time was associated with shorter sleep duration by 0.29 hours in CF and 0.75 hours in non-CF (P = 0.007) and longer sleep latency by 0.15 hours in CF and 0.05 in non-CF (P = 0.035). Among patients with CF, FEV1%, prior acute pulmonary exacerbations and weight were independent of all free-day sleep measurements.

Conclusion  CF in adults is associated with marked delays in sleep phase consistent with circadian rhythm phase delays. Independence from disease characteristics predictive of survival suggests that sleep phase delay is a primary manifestation of CFTR dysfunction in the CNS.

original research 
Samir Soneji, PhD; Nichole T. Tanner, MD, MSCR; Gerard A. Silvestri, MD, MS; Christopher Lathan, MD; William Black, MD
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Background  Black lung cancer patients diagnosed at early stages—for which surgical resection offers a potential cure—experience worse overall survival than their White counterparts. We undertook a population-based study to estimate the racial and ethnic disparity in death from competing causes and assessed its contribution to the gap in overall survival among early-stage lung cancer patients.

Methods  We collected survival time data for 105,121 early-stage (IA, IB, IIA, and IIB) Hispanic, non-Hispanic Asian, non-Hispanic Black, and non-Hispanic White lung cancer patients diagnosed between 2004 and 2013 from the Surveillance, Epidemiology, and End-Results registries. We modeled survival time using competing risk regression and included as covariates sex, age at diagnosis, race/ethnicity, stage at diagnosis, histology, type of surgical resection, and radiation sequence.

Results  Adjusting for demographic, clinical, and treatment characteristics, non-Hispanic Blacks experienced worse overall survival compared to non-Hispanic Whites (adjusted hazard ratio [aHR]: 1.05; 95% confidence interval [CI]: 1.02,1.08) while Hispanics and non-Hispanic Asians experienced better overall survival (aHR=0.93; 95% CI: 0.89, 0.98 and aHR=0.82; 95% CI: 0.79, 0.86, respectively). Worse survival from competing causes of death, such as CVD and other cancers—rather than from lung cancer itself—led to the disparity in overall survival among non-Hispanic Blacks (adjusted relative risk=1.07; 95% CI: 1.02, 1.12).

Conclusions  Narrowing racial and ethnic disparities in survival among early-stage lung cancer patients will rely on more than just equalizing access to surgical resection and will need to include better management and treatment of smoking-related comorbidities and diseases.

contemporary reviews in sleep medicine 
Walter T. McNicholas
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Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSA) are both highly prevalent, which implies that both disorders occurring together (overlap syndrome) is likely to be common based on chance association alone. However, different clinical COPD phenotypes influence the likelihood of co-existing OSA in that the increased lung volumes and low body mass index (BMI) associated with the predominant emphysema phenotype protects against OSA, whereas the higher likelihood of peripheral edema and increased BMI associated with the predominant chronic bronchitis phenotype promotes OSA. Both COPD and OSA are associated with similar physiological and molecular consequences such as hypoxia and systemic inflammation that contribute to cardiovascular and other co-morbidities, and pulmonary hypertension is highly prevalent in patients with the overlap syndrome. However, there have been few published reports that have evaluated systemic inflammation and other cardiovascular co-morbidities in overlap patients. The diagnosis of OSA in patients with COPD requires awareness of relevant clinical features and screening questionnaires may help identify suitable patients for further overnight study. The recognition of co-existing OSA in COPD patients has important clinical relevance as the management of patients with overlap syndrome is different from COPD alone, and the survival of overlap patients not treated with nocturnal positive airway pressure is significantly inferior to those overlap patients appropriately treated.

original research 
Rachel E. Corrado, MS; David Lee, MBA, MPH; David E. Lucero, PhD; Jay K. Varma, MD; Neil M. Vora, MD
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Background  Although pneumonia is a leading cause of death in New York City (NYC), limited data exist about the settings in which pneumonia is acquired across NYC. Pneumonia acquired in community settings are more likely to be preventable with vaccines and treatable with first-line antibiotics than those acquired in non-community settings. Our objective was to estimate the burden of hospitalizations associated with community-acquired (CAP)-, healthcare-associated (HCAP)-, hospital-acquired (HAP)-, and ventilator-associated (VAP) pneumonia during 2010–2014.

Methods  We performed a retrospective analysis of an all-payer reporting system of hospital discharges that included NYC residents aged ≥18 years. Pneumonia-associated hospitalizations were defined as any hospitalization that included a diagnostic code for pneumonia among any of the discharge diagnoses. Using published clinical guidelines, we classified hospitalizations into mutually exclusive categories of CAP, HCAP, HAP, and VAP and defined pneumonia acquired in the community setting as the combination of CAP and HCAP.

Results  Of 4,614,108 hospitalizations during the reporting period, 283,927 (6.2%) involved pneumonia. Among pneumonia-associated hospitalizations, 154,158 (54.3%) were CAP, 85,656 (30.2%) HCAP, 39,712 (14.0%) HAP, and 4,401 (1.6%) VAP. Death during hospitalization occurred in 7.9% of CAP-associated hospitalizations, compared with 15.7% of HCAP-associated hospitalizations, 20.7% of HAP-associated hospitalizations, and 21.6% of VAP-associated hospitalizations.

Conclusions  Most pneumonia-associated hospitalizations in NYC involve pneumonias acquired in the community setting. Only 15.6% of pneumonia-associated hospitalizations were categorized as HAP or VAP, yet these pneumonias accounted for >25% of deaths from pneumonia-associated hospitalizations. Public health pneumonia prevention efforts need to target both community and hospital settings.

special features 
Katharina Ronacher; Reinout van Crevel; Julia Critchley; Andrew A. Bremer; Larry S. Schlesinger; Anil Kapur; Randall Basaraba; Hardy Kornfeld; Blanca I. Restrepo
Topics: , , ,

There is growing interest in the re-emerging interaction between type 2 diabetes (DM) and tuberculosis (TB), but the underlying biological mechanisms are poorly understood despite their possible implications in clinical management. Experts in epidemiological, public health, basic science and clinical studies recently convened and identified research priorities for elucidating the underlying mechanisms for the co-ocurrence of TB and DM. We identified gaps in current knowlege of altered immunity in DM patients during TB, where most studies suggest an under-performing innate immunity, but exaggerated adaptive immunity to Mycobacterium tuberculosis. Various molecular mechanisms and pathways that may underly these observations in the DM host. These include signaling induced by excess advanced glycation end products (AGE) and their receptor (RAGE), higher levels of reactive oxidative species and oxidative stress, epigenetic changes due to chronic hyperglycemia, altered nuclear receptors and/or differences in cell metabolism (immuno-metabolism). Studies in humans at different stages of DM (no DM, pre-DM and DM) or TB (latent or active TB) should be complemented with findings in animal models, which provide the unique opportunity to study early events in the host-pathogen interaction. Such studies could also help identify biomarkers that will complement clinical studies in order to tailor the prevention of TB-DM, or avoid the adverse TB treatment outcomes that are more likely in these patients. Such studies will also inform new approaches to host-directed therapies.

original research 
Wilson A. Quezada, MD; Beth A. Whippo, MSN; Patricia A. Jellen, MSN; Nancy K. Leidy, PhD; David Mannino, MD; Katherine J. Kim, MPH; MeiLan K. Han, MD, MS; Julia F. Houfek, PhD; Barry Make, MD; Karen G. Malley, BA; Catherine A. Meldrum, PhD; Stephen Rennard, MD; Barbara P. Yawn, MD MSc; Fernando Martinez, MD; Byron M. Thomashow, MD
Topics: ,

Background  This study tested the properties of a Spanish translation of CAPTURE™ (COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk) with selective use of peak expiratory flow (PEF).

Methods  Analyses of data from the Spanish-speaking cohort of the cross-sectional, case-control study used to develop CAPTURE. Translation procedures included forward and backward translation, reconciliation, and cognitive interviewing to assure linguistic and cultural equivalence. Spanish-speaking participants were recruited through one center and designated as Cases (clinically significant COPD: FEV1 < 60% predicted and/or at risk of COPD exacerbation) or Controls (No or mild COPD). Subjects completed a questionnaire booklet that included 44 candidate items, COPD Assessment Test (CAT), and modified Medical Research Council (mMRC) dyspnea question. PEF and spirometry were also performed.

Results  N=30 participants: 17 cases; 13 controls. Mean (SD) age: 62.6 (11.49) years; 33% male. CAPTURE-S scores were significantly correlated with PEF (r=-0.78), FEV1/FVC ratio (r=-0.74), FEV1r= (-0.69), FEV1% predicted (r=-0.69), CAT score (r=0.70), and mMRC (r=0.59) (p<0.0001), with significantly higher scores in cases than controls (t=6.16, p<0.0001). PEF significantly correlated with FEV1 (r=0.89), FEV1 % predicted (r=0.79), and FEV1/FVC (r=0.75) (p<0.0001), with significantly lower PEF in cases than controls (t=5.08, p<0.0001). CAPTURE-S score plus PEF differentiated cases and controls with sensitivity = 88.2% and specificity = 92.3%.

Conclusions  CAPTURE-S with selective use of PEF appears to be useful for identifying Spanish-speaking patients in need of diagnostic evaluation for clinically significant COPD who may benefit from initiation of COPD treatment.

original research 
Ying Bai, MD, PhD; Yan-Liang Wang, MD; Alena Shantsila, PhD; Gregory Y.H. Lip, MD, FRCP
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Background  Our previous review showed great variability on the incidence and prevalence of atrial fibrillation (AF) in non-Western cohorts, especially from Asian countries; in recent years, epidemiology studies on AF have been increasingly reported.

Methods  We therefore conducted an updated systematic review, to present the current knowledge base of AF epidemiology in Asian countries since our prior review. We also explored AF incidence and the risk of stroke in AF using meta-analysis, with I2 testing the heterogeneity. Third, ‘real world’ antithrombotic drug use for ischemic stroke (IS) prevention associated with AF was studied.

Results  58 papers from 8 countries in Asia were finally included in our analysis. The summary annual incidence of AF was 5.38 (95% CI: 4.53-6.24, I2=99.5%, N=10) per 1000 person-years and the IS annual risk in AF was 3.0% (1.60%-4.95%, I2=99.8%, N=8) when meta-analysis was performed on hospital- and community-based studies. Hospital- and community- based AF prevalence ranged from 0.37% to 3.56% and 2.8% to 15.8%, respectively. IS prevalence in AF ranged 1.9-6.0% and 0.36-28.3% in community and hospital studies, respectively. Warfarin use in Chinese is relatively low (1.0-4.1%) when compared with Japanese (49.1-70.0%) in community-based studies. The rate of warfarin use was <50% in hospital-based studies.

Conclusions  AF incidence and prevalence has increased in recent years, though great variability still exists in Asian countries. Variability in annual IS risk in AF patients was apparent between hospital- and community-based studies. However, the rate of warfarin use was less than 50% in hospital studies from Asian countries.

original research 
Chien-Cheng Huang, MD; Chung-Han Ho, PhD; Yi-Chen Chen, MS; Hung-Jung Lin, MD, MBA; Chien-Chin Hsu, MD, PhD; Jhi-Joung Wang, MD, PhD; Shih-Bin Su, MD, PhD; How-Ran Guo, MD, MPH, ScD
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Background  To date, there has been no consensus about the effect of hyperbaric oxygen therapy (HBOT) on the mortality of patients with carbon monoxide poisoning (COP). This retrospective nationwide population-based cohort study from Taiwan was conducted to clarify this issue.

Methods  Using the Nationwide Poisoning Database, we identified 25,737 COP patients diagnosed between 1999 and 2012, including 7,278 patients who received HBOT and 18,459 patients who did not. The mortality risks of the two cohorts were compared, including overall mortality, and stratified analyses by age, sex, underlying comorbidities, monthly income, suicide, drug poisoning, acute respiratory failure, and follow-up periods until 2013 were conducted. We also tried to identify independent mortality predictors and evaluated their effects.

Results  Patients who received HBOT had a lower mortality rate compared to patients who did not (adjusted hazard ratio [AHR]: 0.74; 95% confidence interval [CI]: 0.67–0.81) after adjusting for age, sex, underlying comorbidities, monthly income, and concomitant conditions, especially in patients younger than 20 years (AHR: 0.45; 95% CI: 0.26–0.80) and those with acute respiratory failure (AHR: 0.43; 95% CI: 0.35–0.53). The lower mortality rate was noted for a period of 4 years after treatment of COP. Patients who received two or more sessions of HBOT had a lower mortality rate than those who received once only. Older age, male sex, low monthly income, diabetes, malignancy, stroke, alcoholism, mental disorders, suicide attempts, and acute respiratory failure were also independent mortality predictors.

Conclusions  HBOT is associated with a lower mortality rate in patients with COP, especially in those who were younger than 20 years and those with acute respiratory failure. The results provide important references for decision making in the treatment of COP.

original research  FREE TO VIEW
Anand Padmanabhan, MD PhD; Curtis G. Jones, BS; Shannon M. Pechauer, BS; Brian R. Curtis, PhD; Daniel W. Bougie, PhD; Mehraboon S. Irani, MD; Barbara J. Bryant, MD; Jack B. Alperin, MD; Thomas G. Deloughery, MD; Kevin P. Mulvey, MD; Binod Dhakal, MD; Renren Wen, PhD; Demin Wang, PhD; Richard H. Aster, MD
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Background  HIT complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population.

Methods  We describe three HIT patients who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but achieved an immediate and sustained response to intravenous immunoglobulin G (IVIg) therapy. The mechanism of action of IVIg was evaluated in these and in five additional patients with severe HIT. The impact of a common polymorphism (131 H/R) in the platelet IgG receptor, FcγRIIa, on IVIg-mediated inhibition of platelet activation was also examined.

Results  At levels attained in vivo, IVIg inhibits HIT antibody-mediated platelet activation. The constant domain of IgG (Fc) but not the antigen-binding portion (Fab) is required for this effect. Consistent with this finding, IVIg had no effect on HIT antibody binding in a solid phase HIT immunoassay (PF4 ELISA). The R/H131 polymorphism in FcγRIIa influences the susceptibility of platelets to IVIg treatment, with the HH131 genotype being most susceptible to IVIg-mediated inhibition of antibody-induced activation. However, at high doses of IVIg, activation of platelets of all FcγRIIa genotypes was significantly inhibited. All three patients did well on long-term anticoagulation with direct oral anticoagulants (DOACs).

Conclusions  These studies suggest that IVIg treatment should be considered in HIT patients with severe disease refractory to standard therapies.

recent advances in chest medicine 
Rachel M. Presti, MD, PhD; Sonia C. Flores, PhD; Brent E. Palmer, PhD; Jeffrey J. Atkinson, MD; Catherine R. Lesko, PhD; Bryan Lau, PhD; Andrew P. Fontenot, MD; Jesse Roman, MD; John F. McDyer, MD; Homer L. Twigg, III, MD
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Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy (cART) has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for chronic obstructive pulmonary disease, pulmonary hypertension, and lung cancer even in the era of cART. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggest that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage which predisposes PLWH to these conditions. Some of the factors which drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome towards pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH.

special features 
Julia A. Critchley; Blanca I. Restrepo; Katharina Ronacher; Anil Kapur; Andrew A. Bremer; Larry S. Schlesinger; Randall Basaraba; Hardy Kornfeld; Reinout van Crevel
Topics: , , , ,

There is growing interest in the interaction between type 2 diabetes (DM) and tuberculosis (TB), but many research questions remain unanswered. Epidemiologists, basic scientists and clinical experts recently convened and identified priorities. This is the first of two reviews on this topic, summarising priority areas of research with regard to epidemiology, clinical management and public health. First, from an epidemiological point of view, more study is needed to determine the importance of transient hyperglycemia in TB patients, and on the importance of DM for the global epidemic of multi-drug resistant (MDR)-TB. Second, with regard to screening and clinical management of combined TB-DM, clinical trials and large cohort studies should examine the benefits of improved DM care as well as prolonged or intensified TB treatment to the outcome of TB-DM, and investigate cost-effectiveness of screening methods for DM among newly diagnosed TB patients. Third, from a public health and health systems point of view, the population health impact and cost-effectiveness of different interventions to prevent or treat DM and TB in high burden populations should be examined, and health systems interventions should be developed for routine TB-DM screening, management of DM after TB treatment completion, and better access to DM services worldwide. Studies are needed across different ethnicities and settings given the heterogeneity of metabolic perturbations, inflammatory responses, medications, and access to health care. Finally, studies should address interactions between TB, DM and HIV, because of the convergence of epidemics in sub-Saharan Africa and some other parts of the world.

editorial  FREE TO VIEW
Heleen M. Oudemans-van Straaten; Paul W.G. Elbers; Angélique M.E. Spoelstra-de Man
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No abstract is available for this article
point and counterpoint 
Mario F. Perez, MD, MPH; Lori A. Bastian, MD, MPH; Cheryl Oncken, MD, MPH
No abstract is available for this article
point and counterpoint 
Mario F. Perez, MD, MPH; Lori A. Bastian, MD, MPH; Cheryl Oncken, MD, MPH
Topics: , , , , , ,
No abstract is available for this article
point and counterpoint 
Brian Hitsman, PhD; Amanda L. Baker, PhD; Andrea King, PhD
Topics: ,
No abstract is available for this article
point and counterpoint 
Brian Hitsman, PhD; Amanda L. Baker, PhD; Andrea King, PhD
Topics: , , , , , , , , , , , , , ,
No abstract is available for this article
recent advances in chest medicine 
Natalya Azadeh, MD, MPH; Andrew H. Limper, MD; Eva M. Carmona, MD, Ph.D; Jay H. Ryu, MD
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Interstitial lung diseases (ILD) comprise an array of heterogeneous parenchymal lung diseases that are associated with a spectrum of pathologic, radiologic and clinical manifestations. There are ILDs with known etiologies and those that are idiopathic, making treatment strategies challenging. Prognosis can vary according to the type of ILD but many exhibit gradual progression with an unpredictable clinical course in individual patients as seen in idiopathic pulmonary fibrosis and the phenomenon of “acute exacerbation”(AE). Given the often poor prognosis of these patients the search for a reversible cause of respiratory worsening remains paramount. Infections have been theorized to play a role in ILDs; both in the pathogenesis of ILD and as potential triggers of AE. Research efforts thus far have shown the highest association with viral pathogens, however, fungal and bacterial organisms have also been implicated. This review aims to summarize the current knowledge on the role of infections in the setting of ILD.

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