Showing papers in "American Journal of Respiratory and Critical Care Medicine in 2019"
Harvard University1, University of Western Australia2, University of Texas Health Science Center at San Antonio3, McMaster University4, University of Washington5, Centers for Disease Control and Prevention6, University of Utah7, Primary Children's Hospital8, University of Pittsburgh9, University of Michigan10, Vanderbilt University11, University of Connecticut12, United States Department of Veterans Affairs13, Baylor College of Medicine14
TL;DR: Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.
Abstract: Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pra...
1,708 citations
TL;DR: Standards and consensus recommendations are presented for manufacturers, clinicians, operators, and researchers with the aims of increasing the accuracy, precision, and quality of spirometric measurements and improving the patient experience.
Abstract: Background: Spirometry is the most common pulmonary function test. It is widely used in the assessment of lung function to provide objective information used in the diagnosis of lung diseases and monitoring lung health. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for conducting spirometry. Improvements in instrumentation and computational capabilities, together with new research studies and enhanced quality assurance approaches, have led to the need to update the 2005 technical standards for spirometry to take full advantage of current technical capabilities.Methods: This spirometry technical standards document was developed by an international joint task force, appointed by the American Thoracic Society and the European Respiratory Society, with expertise in conducting and analyzing pulmonary function tests, laboratory quality assurance, and developing international standards. A comprehensive review of published evidence was performed. A patient survey was developed to capture patients' experiences.Results: Revisions to the 2005 technical standards for spirometry were made, including the addition of factors that were not previously considered. Evidence to support the revisions was cited when applicable. The experience and expertise of task force members were used to develop recommended best practices.Conclusions: Standards and consensus recommendations are presented for manufacturers, clinicians, operators, and researchers with the aims of increasing the accuracy, precision, and quality of spirometric measurements and improving the patient experience. A comprehensive guide to aid in the implementation of these standards was developed as an online supplement.
1,481 citations
TL;DR: The results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
Abstract: Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
811 citations
TL;DR: In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation.
Abstract: Rationale: One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation.Objectives: To validate the diagnostic...
445 citations
TL;DR: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks’ postmenstrual age, regardless of supplemental oxygen use.
Abstract: Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately pred...
437 citations
TL;DR: Lung ultrasound is a useful diagnostic and monitoring tool that might in the near future become part of the basic knowledge of physicians caring for the critically ill patient.
Abstract: Point-of-care ultrasound is increasingly used at the bedside to integrate the clinical assessment of the critically ill; in particular, lung ultrasound has greatly developed in the last decade. This review describes basic lung ultrasound signs and focuses on their applications in critical care. Lung semiotics are composed of artifacts (derived by air/tissue interface) and real images (i.e., effusions and consolidations), both providing significant information to identify the main acute respiratory disorders. Lung ultrasound signs, either alone or combined with other point-of-care ultrasound techniques, are helpful in the diagnostic approach to patients with acute respiratory failure, circulatory shock, or cardiac arrest. Moreover, a semiquantification of lung aeration can be performed at the bedside and used in mechanically ventilated patients to guide positive end-expiratory pressure setting, assess the efficacy of treatments, monitor the evolution of the respiratory disorder, and help the weaning process. Finally, lung ultrasound can be used for early detection and management of respiratory complications under mechanical ventilation, such as pneumothorax, ventilator-associated pneumonia, atelectasis, and pleural effusions. Lung ultrasound is a useful diagnostic and monitoring tool that might in the near future become part of the basic knowledge of physicians caring for the critically ill patient.
269 citations
TL;DR: The mechanism of action, indications, expected benefits, and side effects of each of the currently approved biologics for severe uncontrolled asthma are reviewed and promising therapeutic targets for the future are discussed.
Abstract: Patients with severe uncontrolled asthma have disproportionally high morbidity and healthcare utilization as compared with their peers with well-controlled disease. Although treatment options for these patients were previously limited, with unacceptable side effects, the emergence of biologic therapies for the treatment of asthma has provided promising targeted therapy for these patients. Biologic therapies target specific inflammatory pathways involved in the pathogenesis of asthma, particularly in patients with an endotype driven by type 2 (T2) inflammation. In addition to anti-IgE therapy that has improved outcomes in allergic asthma for more than a decade, three anti-IL-5 biologics and one anti-IL-4R biologic have recently emerged as promising treatments for T2 asthma. These targeted therapies have been shown to reduce asthma exacerbations, improve lung function, reduce oral corticosteroid use, and improve quality of life in appropriately selected patients. In addition to the currently approved biologic agents, several biologics targeting upstream inflammatory mediators are in clinical trials, with possible approval on the horizon. This article reviews the mechanism of action, indications, expected benefits, and side effects of each of the currently approved biologics for severe uncontrolled asthma and discusses promising therapeutic targets for the future.
258 citations
TL;DR: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB.
Abstract: Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.
254 citations
TL;DR: An in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases; and selected respiratory infections is reported.
Abstract: Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.
239 citations
TL;DR: Understanding the mechanisms of cellular senescence may result in new treatments for chronic lung disease, either by inhibiting PI3K-mTOR signaling, by inhibition of specific miRNAs or by deletion of senescent cells with senolytic therapies, already shown to be effective in experimental lung fibrosis.
Abstract: Cellular senescence is now considered an important driving mechanism for chronic lung diseases, particularly chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Cellular senescence is due to replicative and stress-related senescence with activation of p53 and p16INK4a, respectively, leading to activation of p21CIP1 and cell cycle arrest. Senescent cells secrete multiple inflammatory proteins known as the senescence-associated secretory phenotype, leading to low-grade chronic inflammation, which further drives senescence. Loss of key antiaging molecules sirtuin-1 and sirtuin-6 may be important in acceleration of aging and arises from oxidative stress reducing phosphatase PTEN (phosphatase tensin homolog), thereby activating PI3K (phosphoinositide-3-kinase) and mTOR (mammalian target of rapamycin). MicroRNA-34a (miR-34a), which is regulated by PI3K-mTOR signaling, plays a pivotal role in reducing sirtuin-1/6, and its inhibition with an antagomir results in their restoration, reducing markers of senescence, reducing senescence-associated secretory phenotype, and reversing cell cycle arrest in epithelial cells from peripheral airways of patients with COPD. miR-570 is also involved in reduction of sirtuin-1 and cellular senescence and is activated by p38 mitogen-activated protein kinase. These miRNAs may be released from cells in extracellular vesicles that are taken up by other cells, thereby spreading senescence locally within the lung but also outside the lung through the circulation; this may account for comorbidities of COPD and other lung diseases. Understanding the mechanisms of cellular senescence may result in new treatments for chronic lung disease, either by inhibiting PI3K-mTOR signaling, by inhibiting specific miRNAs, or by deletion of senescent cells with senolytic therapies, already shown to be effective in experimental lung fibrosis.
231 citations
TL;DR: OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.
Abstract: Rationale: Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular...
TL;DR: A comprehensive discussion of the different analytic methods for analyzing and interpreting VFDs, including Student’s t tests and rank-sum tests, as well as competing risk regressions treating extubation as the primary outcome and death as the competing risk.
Abstract: Ventilator-free days (VFDs) are a commonly reported composite outcome measure in acute respiratory distress syndrome trials. VFDs combine survival and duration of ventilation in a manner that summa...
TL;DR: Early norepinephrine was significantly associated with increased shock control by 6 hours in adults diagnosed with sepsis with hypotension and further studies are needed before this approach is introduced in clinical resuscitation practice.
Abstract: Rationale: Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce.Objectives...
University of Paris1, St. Michael's Hospital2, University of Toronto3, ISMETT4, Columbia University5, Hiroshima University6, Alfred Hospital7, Papworth Hospital8, Aix-Marseille University9, Auckland City Hospital10, Cliniques Universitaires Saint-Luc11, St. Vincent's Health System12, Royal Prince Alfred Hospital13, University of Hong Kong14, Harvard University15, Johns Hopkins University16, Pamela Youde Nethersole Eastern Hospital17, University of Maryland, Baltimore18, Paris Diderot University19, French Institute of Health and Medical Research20, Paris Descartes University21, Monash University22
TL;DR: Ultraprotective lung ventilation on ECMO was largely adopted across medium- to high-case volume ECMO centers and did not impact patients' prognosis in this context.
Abstract: Rationale: Current practices regarding mechanical ventilation in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown.Objectives: To report current practices regarding mechanical ventilation in patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and their association with 6-month outcomes.Methods: This was an international, multicenter, prospective cohort study of patients undergoing ECMO for ARDS during a 1-year period in 23 international ICUs.Measurements and Main Results: We collected demographics, daily pre- and per-ECMO mechanical ventilation settings and use of adjunctive therapies, ICU, and 6-month outcome data for 350 patients (mean ± SD pre-ECMO PaO2/FiO2 71 ± 34 mm Hg). Pre-ECMO use of prone positioning and neuromuscular blockers were 26% and 62%, respectively. Vt (6.4 ± 2.0 vs. 3.7 ± 2.0 ml/kg), plateau pressure (32 ± 7 vs. 24 ± 7 cm H2O), driving pressure (20 ± 7 vs. 14 ± 4 cm H2O), respiratory rate (26 ± 8 vs. 14 ± 6 breaths/min), and mechanical power (26.1 ± 12.7 vs. 6.6 ± 4.8 J/min) were markedly reduced after ECMO initiation. Six-month survival was 61%. No association was found between ventilator settings during the first 2 days of ECMO and survival in multivariable analysis. A time-varying Cox model retained older age, higher fluid balance, higher lactate, and more need for renal-replacement therapy along the ECMO course as being independently associated with 6-month mortality. A higher Vt and lower driving pressure (likely markers of static compliance improvement) across the ECMO course were also associated with better outcomes.Conclusions: Ultraprotective lung ventilation on ECMO was largely adopted across medium- to high-case volume ECMO centers. In contrast with previous observations, mechanical ventilation settings during ECMO did not impact patients' prognosis in this context.
TL;DR: It is demonstrated that lung microbiota contribute to the progression of IPF, providing biological plausibility for the hypothesis that lung dysbiosis promotes alveolar inflammation and aberrant repair and Manipulation of lung microbiota may represent a novel target for the treatment of IPf.
Abstract: Rationale: Idiopathic pulmonary fibrosis (IPF) causes considerable global morbidity and mortality, and its mechanisms of disease progression are poorly understood. Recent observational studies have reported associations between lung dysbiosis, mortality, and altered host defense gene expression, supporting a role for lung microbiota in IPF. However, the causal significance of altered lung microbiota in disease progression is undetermined. Objectives: To examine the effect of microbiota on local alveolar inflammation and disease progression using both animal models and human subjects with IPF. Methods: For human studies, we characterized lung microbiota in BAL fluid from 68 patients with IPF. For animal modeling, we used a murine model of pulmonary fibrosis in conventional and germ-free mice. Lung bacteria were characterized using 16S rRNA gene sequencing with novel techniques optimized for low-biomass sample load. Microbiota were correlated with alveolar inflammation, measures of pulmonary fibrosis, and disease progression. Measurements and Main Results: Disruption of the lung microbiome predicts disease progression, correlates with local host inflammation, and participates in disease progression. In patients with IPF, lung bacterial burden predicts fibrosis progression, and microbiota diversity and composition correlate with increased alveolar profibrotic cytokines. In murine models of fibrosis, lung dysbiosis precedes peak lung injury and is persistent. In germ-free animals, the absence of a microbiome protects against mortality. Conclusions: Our results demonstrate that lung microbiota contribute to the progression of IPF. We provide biological plausibility for the hypothesis that lung dysbiosis promotes alveolar inflammation and aberrant repair. Manipulation of lung microbiota may represent a novel target for the treatment of IPF.
TL;DR: Results are promising for the use of ventilatory ratio as a simple bedside index of impaired ventilation in ARDS, and higher values at baseline are associated with increased risk of adverse outcomes.
Abstract: Rationale: Pulmonary dead space fraction (Vd/Vt) is an independent predictor of mortality in acute respiratory distress syndrome (ARDS) Yet, it is seldom used in practice The ventilatory ratio is
TL;DR: In normal/healthy human airways, MUC5B is the dominant secretory mucin in the superficial epithelium and glands, with distal airways being a major site of expression.
Abstract: Rationale: MUC5AC and MUC5B are the predominant gel-forming mucins in the mucus layer of human airways. Each mucin has distinct functions and site-specific expression. However, the regional distrib...
TL;DR: A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on 1 night greatly reduced OSA severity and genioglossus responsiveness, and open new possibilities for the pharmacologic treatment of OSA.
Abstract: Rationale: There is currently no effective pharmacological treatment for obstructive sleep apnea (OSA). Recent investigations indicate that drugs with noradrenergic and antimuscarinic effects impro...
TL;DR: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration, but conflicting survival effects as mentioned in this paper, and two transcriptome-based SEPSIS responses were found to be correlated with the use of these drugs.
Abstract: Rationale: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration, but conflicting survival effects. Two transcriptomic sepsis respons...
TL;DR: The results provide new evidence that short-term exposures to PM2.5, NO2 and O3 may increase asthma mortality risk and further studies are needed to confirm the findings in other populations.
Abstract: Rationale: Short-term exposure to air pollution has been associated with asthma exacerbation and increased healthcare use caused by asthma, but its effect on asthma mortality remains largely unknown. Objectives: To quantitatively assess the association between short-term exposure to air pollution and asthma mortality. Methods: We investigated 4,454 individuals who lived in Hubei province, China, and died from asthma between 2013 and 2018. A case-crossover design and conditional logistic regression models were applied for data analyses. Exposures to particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), particulate matter ≤10 μm in aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were estimated by inverse distance weighted averages of all monitoring stations within 50 km from each case's home address. Measurements and Main Results: Each interquartile range (IQR) increase of PM2.5 (lag 3; IQR, 47.1 μg/m3), NO2 (lag 03; IQR, 26.3 μg/m3), and O3 (lag 3; IQR, 52.9 μg/m3) were positively associated with asthma mortality, with odds ratios of 1.07 (95% confidence interval, 1.01-1.12), 1.11 (95% confidence interval, 1.01-1.22), and 1.09 (95% confidence interval, 1.01-1.18), respectively. There was no evidence of departure from linearity for these associations. Further adjustment for other pollutants did not change the associations materially. We did not observe significant associations between PM10, SO2, and CO exposures and asthma mortality. Overall, the estimates remained consistent in various sensitivity analyses. Conclusions: Our results provide new evidence that short-term exposures to PM2.5, NO2, and O3 may increase asthma mortality risk. Further studies are needed to confirm our findings in other populations.
TL;DR: The burden of uncontrolled asthma is substantial and will continue to grow, and better adherence to evidence-informed asthma management strategies by care providers and patients has the potential to substantially reduce costs and improve quality of life.
Abstract: Rationale: Despite effective treatments, a large proportion of patients with asthma do not achieve sustained asthma control. The "preventable" burden associated with lack of proper control is likely taking a high toll at the personal and population level.Objectives: We predicted the future excess health and economic burden associated with uncontrolled asthma among American adolescents and adults for the next 20 years.Methods: We built a probabilistic model that linked state-specific estimates of population growth, aging, asthma prevalence, and asthma control levels. We conducted several meta-analyses to estimate the adjusted differences in healthcare resource use, quality-adjusted life years (QALYs), and productivity loss across control levels. We projected, nationally and at the state level, total direct and indirect (due to productivity loss) costs (in 2018 dollars) and QALYs lost because of uncontrolled asthma from 2019 to 2038.Measurements and Main Results: Total 20-year direct costs associated with uncontrolled asthma are estimated to be $300.6 billion (95% confidence interval [CI], $190.1 billion-411.1 billion). When indirect costs are added, total economic burden will be $963.5 billion (95% CI, $664.1 billion-1,262.9 billion). American adolescents and adults will lose an estimated 15.46 million (95% CI, 12.77 million-18.14 million) QALYs over this period because of uncontrolled asthma. Across states, the average 20-year per capita costs due to uncontrolled asthma ranged from $2,209 (Arkansas) to $6,132 (Connecticut).Conclusions: The burden of uncontrolled asthma is substantial and will continue to grow. Given that a substantial fraction of this burden is preventable, better adherence to evidence-informed asthma management strategies by care providers and patients has the potential to substantially reduce costs and improve quality of life.
TL;DR: High extracellular DNA concentrations in sputum mark a subset of patients with more severe asthma who have NETs and markers of inflammasome activation in their airways, as well as in in vitro studies, NETs caused cytotoxicity in airway epithelial cells that was prevented by disruption of NETs with DNase.
Abstract: Rationale: Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation and IL-1β secretion from monocytes and cause airway epithelial cell injury, but the role of eDNA, NETs, and IL-1β in asthma is uncertain. Objectives: To characterize the role of activated neutrophils in severe asthma through measurement of NETs and inflammasome activation. Methods: We measured sputum eDNA in induced sputum from 399 patients with asthma in the Severe Asthma Research Program-3 and in 94 healthy control subjects. We subdivided subjects with asthma into eDNA-low and -high subgroups to compare outcomes of asthma severity and of neutrophil and inflammasome activation. We also examined if NETs cause airway epithelial cell damage that can be prevented by DNase. Measurements and Main Results: We found that 13% of the Severe Asthma Research Program-3 cohort is "eDNA-high," as defined by sputum eDNA concentrations above the upper 95th percentile value in health. Compared with eDNA-low patients with asthma, eDNA-high patients had lower Asthma Control Test scores, frequent history of chronic mucus hypersecretion, and frequent use of oral corticosteroids for maintenance of asthma control (all P values <0.05). Sputum eDNA in asthma was associated with airway neutrophilic inflammation, increases in soluble NET components, and increases in caspase 1 activity and IL-1β (all P values <0.001). In in vitro studies, NETs caused cytotoxicity in airway epithelial cells that was prevented by disruption of NETs with DNase. Conclusions: High extracellular DNA concentrations in sputum mark a subset of patients with more severe asthma who have NETs and markers of inflammasome activation in their airways.
TL;DR: Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD, while SLBs were more frequently concordants with the final diagnosis retained at MDA.
Abstract: Rationale: The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)—versus surgical lung biopsy (SLB) as the current gold standard—in interstitial lung disease (ILD) cases requiring...
TL;DR: Chronic vaping disrupts the protease-antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease and indicates that vaping may not be safer than tobacco smoking.
Abstract: Rationale: Proteolysis is a key aspect of the lung’s innate immune system. Proteases, including neutrophil elastase and MMPs (matrix metalloproteases), modulate cell signaling, inflammation, tissue...
TL;DR: The mere presence of ILD at baseline appears to affect outcome in SSc, suggesting that all SSc patients should undergo baseline PFT and lung HRCT screening to diagnose ILD early and tailor further management.
Abstract: Rationale: Interstitial lung disease (ILD) represents a major challenge in systemic sclerosis (SSc), but there are no precise, population-based data on its overall impact, limiting opportunities fo...
TL;DR: The apnea-hypopnea index does not capture the range of sleep apnea as discussed by the authors, which is a poor risk predictor for mortality, since it does not represent the full spectrum of sleep disorders.
Abstract: Rationale: Obstructive sleep apnea is a risk factor for mortality, but its diagnostic metric—the apnea–hypopnea index—is a poor risk predictor. The apnea–hypopnea index does not capture the range o...
TL;DR: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.
Abstract: Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.
TL;DR: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.
Abstract: Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although...
TL;DR: The best evidence is applied from animal and human studies to highlight the relationship between OSA and nonalcoholic fatty liver disease and to advocate for further trials aimed at defining these relationships more precisely.
Abstract: Recent studies have demonstrated that obstructive sleep apnea (OSA) is associated with the development and evolution of nonalcoholic fatty liver disease (NAFLD), independent of obesity or other shared risk factors. Like OSA, NAFLD is a prevalent disorder associated with major adverse health outcomes: Patients with NAFLD may develop cirrhosis, liver failure, and hepatocellular carcinoma. One major finding that has emerged from these studies is that the OSA-NAFLD association is related to the degree of nocturnal hypoxemia in OSA. Animal models have therefore largely focused on intermittent hypoxia, a key manifestation of OSA, to shed light on the mechanisms by which OSA may give rise to the complex metabolic disturbances that are seen in NAFLD. Intermittent hypoxia leads to tissue hypoxia and can result in oxidative stress, mitochondrial dysfunction, inflammation, and overactivation of the sympathetic nervous system, among many other maladaptive effects. In such models, intermittent hypoxia has been shown to cause insulin resistance, dysfunction of key steps in hepatic lipid metabolism, atherosclerosis, and hepatic steatosis and fibrosis, each of which is pertinent to the development and/or progression of NAFLD. However, many intriguing questions remain unanswered: Principally, how aggressively should the clinician screen for NAFLD in patients with OSA, and vice versa? In this review, we attempt to apply the best evidence from animal and human studies to highlight the relationship between these two disorders and to advocate for further trials aimed at defining these relationships more precisely.
TL;DR: This guideline includes specific recommendations on the use of galactomannan testing in serum and BAL and the role of PCR in the diagnosis of invasive pulmonary aspergillosis, and the application of serology and antigen testing in thediagnosis of the endemic mycoses.
Abstract: Background: Fungal infections are of increasing incidence and importance in immunocompromised and immunocompetent patients. Timely diagnosis relies on appropriate use of laboratory testing in susceptible patients.Methods: The relevant literature related to diagnosis of invasive pulmonary aspergillosis, invasive candidiasis, and the common endemic mycoses was systematically reviewed. Meta-analysis was performed when appropriate. Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation approach.Results: This guideline includes specific recommendations on the use of galactomannan testing in serum and BAL and for the diagnosis of invasive pulmonary aspergillosis, the role of PCR in the diagnosis of invasive pulmonary aspergillosis, the role of β-d-glucan assays in the diagnosis of invasive candidiasis, and the application of serology and antigen testing in the diagnosis of the endemic mycoses.Conclusions: Rapid, accurate diagnosis of fungal infections relies on appropriate application of laboratory testing, including antigen testing, serological testing, and PCR-based assays.