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Turning Sarkoid into Dropsy: A Valiant, Next-Generation Attempt.
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Turning Sarkoid into Dropsy: A Valiant, Next-Generation Attempt.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Dickson RP

Abstract
n/a.

PMID: 28930643 [PubMed - as supplied by publisher]




Face Masks and Cough Etiquette Reduce the Cough Aerosol Concentration of Pseudomonas aeruginosa in People with Cystic Fibrosis.
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Face Masks and Cough Etiquette Reduce the Cough Aerosol Concentration of Pseudomonas aeruginosa in People with Cystic Fibrosis.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Wood ME, Stockwell RE, Johnson GR, Ramsay KA, Sherrard LJ, Jabbour N, Ballard E, O'Rourke P, Kidd TJ, Wainwright CE, Knibbs LD, Sly PD, Morawska L, Bell SC

Abstract
RATIONALE: People with cystic fibrosis (CF) generate Pseudomonas aeruginosa in droplet nuclei during coughing. The use of surgical masks has been recommended in healthcare settings to minimise pathogen transmission between CF patients.
OBJECTIVE: To determine if face masks and cough etiquette reduce viable P. aeruginosa aerosolised during cough.
METHODS: Twenty-five adults with CF and chronic P. aeruginosa infection were recruited. Participants performed six talking and coughing maneuvers, with or without face masks (surgical and N95) and hand covering the mouth when coughing (cough etiquette) in an aerosol-sampling device. An Andersen Impactor sampled the aerosol at 2-meters from each participant. Quantitative sputum and aerosol bacterial cultures were performed and participants rated the mask comfort levels during the cough maneuvers.
MEASUREMENTS AND MAIN RESULTS: During uncovered coughing (reference maneuver), 19/25 (76%) participants produced aerosols containing P. aeruginosa, with a positive correlation found between sputum P. aeruginosa concentration (CFU/mL) and aerosol P. aeruginosa CFUs. There was a reduction in aerosol P. aeruginosa load during coughing with surgical mask, coughing with N95 mask and cough etiquette compared with uncovered coughing (p<0.001). A similar reduction in total CFUs was observed for both masks during coughing, yet participants rated surgical masks more comfortable (p=0.013). Cough etiquette provided approximately half the reduction of viable aerosols of the mask interventions during voluntary cough. Talking was a low viable aerosol producing activity.
CONCLUSIONS: Face masks reduce cough generated P. aeruginosa aerosols, with the surgical mask providing enhanced comfort. Cough etiquette was less effective at reducing viable aerosols.

PMID: 28930641 [PubMed - as supplied by publisher]




50 Years of Research in ARDS. Tidal Volume Selection in the Acute Respiratory Distress Syndrome.
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50 Years of Research in ARDS. Tidal Volume Selection in the Acute Respiratory Distress Syndrome.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Sahetya SK, Mancebo J, Brower RG

Abstract
Mechanical ventilation (MV) is critical in the management of many patients with the acute respiratory distress syndrome (ARDS). However, MV can also cause ventilator-induced lung injury (VILI). The selection of an appropriate tidal volume is an essential part of a lung-protective MV strategy. Since the publication of a large randomized clinical trial demonstrating the benefit of lower tidal volumes, the use of tidal volumes of 6 mL/kg predicted body weight (PBW, based on sex and height) has been recommended in clinical practice guidelines. However, the PBW approach is imperfect in ARDS patients because the amount of aerated lung varies considerably due to differences in inflammation, consolidation, flooding, and atelectasis. Better approaches to setting tidal volume may include limits on end-inspiratory transpulmonary pressure, lung strain, and driving pressure. The limits of lowering tidal volume have not yet been established, and some patients may benefit from tidal volumes that are lower than those in current use. However, lowering tidal volumes may result in respiratory acidosis. Tactics to reduce respiratory acidosis include reductions in ventilation circuit dead space, increases in respiratory rate, higher positive end-expiratory pressures (PEEP) in patients who recruit lung in response to PEEP, recruitment maneuvers, and prone positioning. Mechanical adjuncts such as extracorporeal carbon dioxide removal may be useful to normalize pH and carbon dioxide levels, but further studies will be necessary to demonstrate benefit with this technology.

PMID: 28930639 [PubMed - as supplied by publisher]




Fetal and Infant Growth Patterns and Risk of Lower Lung Function and Asthma. The Generation R Study.
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Fetal and Infant Growth Patterns and Risk of Lower Lung Function and Asthma. The Generation R Study.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: den Dekker HT, Jaddoe VWV, Reiss IK, de Jongste JC, Duijts L

Abstract
BACKGROUND: Children with lower birth weight are at increased risk of asthma symptoms. We examined associations of fetal and infant growth with childhood lung function and asthma.
METHODS: This study was embedded in a population-based prospective cohort study among 5,635children. Growth was estimated by repeated ultrasounds in 2nd and 3th trimester, and measured at birth and at 3, 6 and 12 months. At age 10 years, spirometry was performed and asthma was assessed by parental questionnaire. Restricted and accelerated growth were defined as growth percentile change between time periods of <-0.67 and >0.67 SDS, respectively. We applied multiple regression analyses, including conditional, accounting for correlations between repeated growth measures.
RESULTS: Overall greater weight in 2nd and 3th trimester, at birth and 12 months were associated with higher FEV1 and FVC (range z-score difference: 0.04 - 0.08, per SDS weight increase), not asthma, while greater weight at 3 months was with lower FEV1/FVC and FEF75 (z-score differences (95% CI): -0.09 (-0.14, -0.05) and -0.09 (-0.13, -0.05), per SDS weight increase). Restricted fetal weight growth was associated with lower FEV1, FVC, FEV1/FVC, FEF25-75 and FEF75, partly dependent of infant weight growth patterns (range z-score difference: -0.25 - -0.13). Accelerated fetal weight growth was associated with higher FVC and lower FEV1/FVC only if followed by accelerated infant weight growth.
CONCLUSION: Both restricted fetal weight growth, partly dependent of infant weight growth, and accelerated fetal and infant weight growth predispose children for lower lung function and potential risk for later life chronic obstructive respiratory diseases.

PMID: 28930491 [PubMed - as supplied by publisher]




Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.
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Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Donaldson SH, Pilewski JM, Griese M, Cooke J, Viswanathan L, Tullis E, Davies JC, Lekstrom-Himes JA, Wang LT, VX11-661-101 Study Group

Abstract
RATIONALE: Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor.
OBJECTIVES: To evaluate safety and efficacy of tezacaftor monotherapy and tezacaftor/ivacaftor combination therapy in subjects with CF homozygous for F508del or compound heterozygous for F508del and G551D.
METHODS: This was a randomized, placebo-controlled, double-blind, multicenter, phase 2 study (NCT01531673). Subjects homozygous for F508del received tezacaftor (10 mg to 150 mg) qday alone or in combination with ivacaftor 150 mg q12h in a dose escalation phase, as well as in a dosage regimen testing phase. Subjects compound heterozygous for F508del and G551D taking physician prescribed ivacaftor received tezacaftor 100 mg qday.
MEASUREMENTS AND MAIN RESULTS: Primary endpoints were safety through day 56 and change in sweat chloride from baseline through day 28. Secondary endpoints included change in percent predicted FEV1 (ppFEV1) from baseline through day 28 and pharmacokinetics. The incidence of adverse events was similar across treatment arms. Tezacaftor 100 mg qday/ivacaftor 150 mg q12h resulted in a 6.04 mmol/L decrease in sweat chloride and 3.75 percentage point increase in ppFEV¬1 in subjects homozygous for F508del and a 7.02 mmol/L decrease in sweat chloride and 4.60 percentage point increase in ppFEV¬1 in subjects compound heterozygous for F508del and G551D from baseline through day 28 (P < 0.05 for all).
CONCLUSIONS: These results support continued clinical development of tezacaftor 100 mg qday in combination with ivacaftor 150 mg q12h in subjects with CF. Clinical trial registration available at www.clinicaltrials.gov, ID NCT0153167.

PMID: 28930490 [PubMed - as supplied by publisher]




Emerging Roles of Inflammasomes in Acute Pneumonia.
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Emerging Roles of Inflammasomes in Acute Pneumonia.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Kumar SR, Paudel S, Ghimire L, Bergeron S, Cai S, Zemans RL, Downey GP, Jeyaseelan S

Abstract
Pneumonia is responsible for a substantial burden on healthcare worldwide and the single largest cause for death of infants globally. Pneumonia is caused by a variety of pathogenic microorganisms including bacteria, viruses and fungi. The lung has developed complex innate immune mechanisms to combat these infections while minimizing tissue damage. One essential mechanism that drives the initial innate immune response is sensing a broad spectrum of stimuli in the cytosol by inflammasomes. Inflammasomes are composed of NLR and non-NLR proteins, and activate caspase-1 that results in proinflammatory cytokine activation. When insufficiently controlled, inflammasome activation in the lung leads to extensive inflammation and excessive tissue damage. The aim of this review is to highlight recent advances that illuminate on the roles of inflammasomes and their signaling cascades in acute microbial pneumonia. We also discuss unanswered questions and current controversies associated with inflammasome functions and implications in acute pneumonia. Ultimately, understanding the molecular and cellular mechanisms associated with inflammasome signaling in the lung is potentially important for the development of novel and effective strategies to control pneumonia, and its associated pathologies and the untoward consequences of unchecked inflammation.

PMID: 28930487 [PubMed - as supplied by publisher]




Therapeutic Value of ASK1 Inhibition in Pulmonary Arterial Hypertension.
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Therapeutic Value of ASK1 Inhibition in Pulmonary Arterial Hypertension.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Boucherat O, Provencher S, Bonnet S

PMID: 28930485 [PubMed - as supplied by publisher]




Apoptosis Signal-regulating Kinase 1 Inhibition in Pulmonary Hypertension: Too Much to ASK?
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Apoptosis Signal-regulating Kinase 1 Inhibition in Pulmonary Hypertension: Too Much to ASK?

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Wilkins MR

PMID: 28930481 [PubMed - as supplied by publisher]




The Case of Missing Airways in COPD.
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The Case of Missing Airways in COPD.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Diaz AA

PMID: 28930479 [PubMed - as supplied by publisher]




Mechanical Ventilation-induced Diaphragm Atrophy Strongly Impacts Clinical Outcomes.
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Mechanical Ventilation-induced Diaphragm Atrophy Strongly Impacts Clinical Outcomes.

Am J Respir Crit Care Med. 2017 Sep 20;:

Authors: Goligher EC, Dres M, Fan E, Rubenfeld GD, Scales DC, Herridge MS, Vorona S, Sklar MC, Rittayamai N, Lanys A, Murray A, Brace D, Urrea C, Reid WD, Tomlinson G, Slutsky AS, Kavanagh BP, Brochard LJ, Ferguson ND

Abstract
Rationale Diaphragm dysfunction worsens outcomes in mechanically ventilated patients but the clinical impact of potentially preventable changes in diaphragm structure and function due to mechanical ventilation is unknown. Objectives To determine whether diaphragm atrophy developing during mechanical ventilation leads to prolonged ventilation. Methods Diaphragm thickness was measured daily by ultrasound in adults requiring invasive mechanical ventilation; inspiratory effort was assessed by thickening fraction. The primary outcome was time to liberation from ventilation. Secondary outcomes included complications (reintubation, tracheostomy, prolonged ventilation, or death). Associations were adjusted for age, severity of illness, sepsis, sedation, neuromuscular blockade, and comorbidity. Measurements and Main Results Of 211 patients enrolled, 191 had two or more diaphragm thickness measurements. Thickness decreased more than 10% in 78 patients (41%) by median day 4 (IQR 3-5). Development of decreased thickness was associated with a lower daily probability of liberation from ventilation (adjusted HR 0.69, 95%CI 0.54-0.87, per 10% decrease), prolonged ICU admission (duration ratio 1.71, 95%CI 1.29-2.27), and a higher risk of complications (OR 3.00, 95%CI 1.34-6.72). Development of increased thickness (n=47, 24%) also predicted prolonged ventilation (duration ratio 1.38, 95%CI 1.00-1.90). Decreasing thickness was related to abnormally low inspiratory effort; increasing thickness was related to excessive effort. Patients with thickening fraction between 15-30% (similar to breathing at rest) during the first 3 days had the shortest duration of ventilation. Conclusions Diaphragm atrophy developing during mechanical ventilation strongly impacts clinical outcomes. Targeting an inspiratory effort level similar to that of healthy subjects at rest might accelerate liberation from ventilation.

PMID: 28930478 [PubMed - as supplied by publisher]