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Neutrophil Elastase Activity is Associated with Exacerbations and Lung Function Decline in Bronchiectasis.

Neutrophil Elastase Activity is Associated with Exacerbations and Lung Function Decline in Bronchiectasis.

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Chalmers JD, Moffitt KL, Suarez-Cuartin G, Sibila O, Finch S, Furrie E, Dicker A, Wrobel K, Elborn JS, Walker B, Martin SL, Marshall SE, Huang JT, Fardon TC

Abstract
RATIONALE: Sputum neutrophil elastase and serum desmosine, a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis.
METHODS: This was a single-centre prospective cohort study using the TAYBRIDGE registry in Dundee, UK. 433 patients with HRCT-confirmed bronchiectasis provided blood samples for desmosine measurement and 381 provided sputum for baseline elastase activity measurements using an activity based immunosassay and fluorometric substrate assay. Candidate biomarkers were tested for their relationship with cross-sectional markers of disease severity, and with future exacerbations, mortality and lung function decline over 3-years.
RESULTS: Elastase activity in sputum was associated with the bronchiectasis severity index (r=0.49,p<0.0001) and also correlated with MRC dyspnoea score (r=0.34,p<0.0001), FEV1 % predicted (r=-0.33,p<0.0001) and the radiological extent of bronchiectasis (r=0.29,p<0.0001). During 3-years follow-up, elevated sputum elastase activity was associated with a higher frequency of exacerbations (p<0.0001) but was not independently associated with mortality. Sputum elastase activity was independently associated with FEV1 decline (beta coefficient -0.139,p=0.001). Elastase showed good discrimination for severe exacerbations AUC 0.75 (0.72-0.79) and all-cause mortality AUC 0.70 (0.67-0.73) Sputum elastase activity increased at exacerbation (p=0.001) and was responsive to treatment with antibiotics. Desmosine was correlated with sputum elastase (r=0.34,p<0.0001), and was associated with risk of severe exacerbations HR 2.7 (1.42-5.29),p=0.003, but not lung function decline.
CONCLUSIONS: Sputum neutrophil elastase activity is a biomarker of disease severity and future risk in adults with bronchiectasis.

PMID: 27911604 [PubMed - as supplied by publisher]




Recommended Reading from University of Georgia Department of Epidemiology and Biostatistics Fellows.

Recommended Reading from University of Georgia Department of Epidemiology and Biostatistics Fellows.

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Martinez L, Castellanos ME, Hallowell BD, Whalen CC

PMID: 27911589 [PubMed - as supplied by publisher]




Effects of Variable Pressure Support Ventilation on Regional Homogeneity and Aeration.

Effects of Variable Pressure Support Ventilation on Regional Homogeneity and Aeration.

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Mauri T, Lazzeri M, Bronco A, Bellani G, Pesenti A

PMID: 27911587 [PubMed - as supplied by publisher]




Early Lung Disease in Infants and Pre-school Children with Cystic Fibrosis: What Have We Learnt and What Should We Do About It?

Early Lung Disease in Infants and Pre-school Children with Cystic Fibrosis: What Have We Learnt and What Should We Do About It?

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Ranganathan SC, Hall GL, Sly PD, Stick SM, Douglas TA, Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF)

Abstract
The past decade has seen significant advances in understanding of the pathogenesis and progression of lung disease in cystic fibrosis. Pulmonary inflammation, infection and structural lung damage manifest very early in life and is prevalent among preschool children and infants, often in the absence of symptoms or signs. Early childhood represents a pivotal period amenable to intervention strategies that could delay or prevent the onset of lung damage and alter the longer term clinical trajectory for individuals with CF. This review summarizes what we have learnt about early lung disease in children with CF and discusses the implications for future clinical practice and research.

PMID: 27911585 [PubMed - as supplied by publisher]




Recommended Reading from Northwestern University Fellows.

Recommended Reading from Northwestern University Fellows.

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Walter JM, Kruser J, Reyfman P, Sporn PH

PMID: 27911582 [PubMed - as supplied by publisher]




Recommended Reading from Mayo Clinic, Department of Pulmonary and Critical Care Medicine Fellows.

Recommended Reading from Mayo Clinic, Department of Pulmonary and Critical Care Medicine Fellows.

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Azadeh N, Clay RD, Braus NA, Ramar K

PMID: 27911567 [PubMed - as supplied by publisher]




Pedometer Step Count Targets During Pulmonary Rehabilitation in COPD: A Randomized Controlled Trial.

Pedometer Step Count Targets During Pulmonary Rehabilitation in COPD: A Randomized Controlled Trial.

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Nolan CM, Maddocks M, Canavan JL, Jones SE, Delogu V, Kaliaraju D, Banya W, Kon SS, Polkey MI, Man WD

Abstract
RATIONALE: Increasing physical activity is a key therapeutic aim in COPD. Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence regarding its ability to improve physical activity levels.
OBJECTIVE: To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate intensity physical activity (time ≥ 3METs) in people with COPD.
METHODS: In this single-blinded randomized controlled trial, participants were assigned 1:1 to receive control (PR comprising 8 weeks, two supervised sessions/week) or intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 weeks). The randomisation process used minimisation to balance groups for age, sex, FEV1 % predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was by intention-to-treat and the trial registered with clinicaltrials.gov (Ref. NCT01719822).
MEASUREMENTS: The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time ≥3METs.
MAIN RESULTS: 152 participants (72% male; mean (SD) FEV1 % predicted 50.5 (21.2); median (Q1, Q3) time ≥3METS 46 (21, 92) minutes) were enrolled to intervention (n=76) or control (n=76). There was no significant difference in change in time ≥3METs between the intervention and control groups at 8 weeks (median (Q1, Q3) difference 0.5 (-1.0, 31.0) minutes; p=0.87) or at the 6 month follow-up (7.0 (-9, 27) minutes; p=0.16).
CONCLUSION: Pedometer-directed step count targets during an outpatient PR program did not enhance moderate intensity physical activity levels in people with COPD. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01719822.

PMID: 27911566 [PubMed - as supplied by publisher]




SIgA Deficiency in Individual Small Airways is Associated with Persistent Inflammation and Remodeling.

SIgA Deficiency in Individual Small Airways is Associated with Persistent Inflammation and Remodeling.

Am J Respir Crit Care Med. 2016 Dec 02;

Authors: Polosukhin VV, Richmond BW, Du RH, Cates JM, Wu P, Nian H, Massion PP, Ware LB, Lee JW, Kononov AV, Lawson WE, Blackwell TS

Abstract
RATIONALE: Maintenance of a surface immune barrier is important for homeostasis in organs with mucosal surfaces that interface with the external environment; however, the role of the mucosal immune system in chronic lung diseases is incompletely understood.
OBJECTIVES: We examined the relationship between secretory immunoglobulin A (SIgA) on the mucosal surface of small airways and parameters of inflammation and airway wall remodeling in chronic obstructive pulmonary disease (COPD).
METHODS: We studied 1,104 small airways (<2 mm in diameter) from 50 former smokers with COPD and 39 control subjects. Small airways were identified on serial tissue sections and examined for epithelial morphology, SIgA, bacterial DNA, NF-κB activation, neutrophil and macrophage infiltration, and airway wall thickness.
MEASUREMENTS AND MAIN RESULTS: Morphometric evaluation of small airways revealed increased mean airway wall thickness and inflammatory cell counts in lungs from COPD patients compared to control subjects, while SIgA level on the mucosal surface was decreased. However, when small airways were classified as SIgA-intact or SIgA-deficient, we found that pathological changes were localized almost exclusively to SIgA-deficient airways, regardless of study group. SIgA-deficient airways were characterized by: 1) abnormal epithelial morphology, 2) invasion of bacteria across the apical epithelial barrier, 3) NF κB activation, 4) accumulation of macrophages and neutrophils, and 5) fibrotic remodeling of the airway wall.
CONCLUSIONS: Our findings support the concept that localized, acquired SIgA deficiency in individual small airways of COPD patients allows colonizing bacteria to cross the epithelial barrier and drive persistent inflammation and airway wall remodeling, even after smoking cessation.

PMID: 27911098 [PubMed - as supplied by publisher]




Menopause is Associated with Accelerated Lung Function Decline.
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Menopause is Associated with Accelerated Lung Function Decline.

Am J Respir Crit Care Med. 2016 Dec 1;

Authors: Triebner K, Matulonga B, Johannessen A, Suske S, Benediktsdóttir B, Demoly P, Dharmage SC, Franklin KA, Garcia Aymerich J, Gullón Blanco JA, Heinrich J, Holm M, Jarvis D, Jõgi R, Lindberg E, Moratalla Rovira JM, Muniozguren Agirre N, Pin I, Probst-Hensch N, Puggini L, Raherison C, Sánchez-Ramos JL, Schlünssen V, Sunyer J, Svanes C, Hustad S, Leynaert B, Real FG

Abstract
RATIONALE: Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause.
OBJECTIVES: To study whether lung function decline, assessed by forced vital capacity and forced expiratory volume in one second, is accelerated in women who undergo menopause.
METHODS: The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry and questionnaire data about respiratory and reproductive health from three study waves (N=1438). We measured follicle stimulating hormone and luteinizing hormone and added information on menstrual patterns, to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, packyears, current smoking, age at completed full-time education, spirometer and including study center as random effect.
MEASUREMENTS AND MAIN RESULTS: Menopausal status was associated with accelerated lung function decline. The adjusted mean forced vital capacity decline was increased by -10.2 ml/yr (95% Confidence interval -13.1 to -7.2) in transitional women and -12.5 ml/yr (-16.2 to -8.9) in postmenopausal women, compared to women menstruating regularly. The adjusted mean forced expiratory volume in one second decline increased by -3.8 ml/yr (-6.3 to -2.9) in transitional women and -5.2 ml/yr (-8.3 to -2.0) in postmenopausal women.
CONCLUSIONS: Lung function declined more rapidly among transitional and postmenopausal women, in particular for forced vital capacity, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

PMID: 27907454 [PubMed - as supplied by publisher]




Reply: Promise and Limitations of Relaxin-based Therapies in Chronic Fibrotic Lung Diseases.
Related Articles

Reply: Promise and Limitations of Relaxin-based Therapies in Chronic Fibrotic Lung Diseases.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1435-1436

Authors: Tan J, Kass DJ

PMID: 27905855 [PubMed - in process]




Promise and Limitations of Relaxin-based Therapies in Chronic Fibrotic Lung Diseases.
Related Articles

Promise and Limitations of Relaxin-based Therapies in Chronic Fibrotic Lung Diseases.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1434-1435

Authors: Royce SG, Bathgate RA, Samuel CS

PMID: 27905854 [PubMed - in process]




Surprising Results from an Angiotensin-Converting Enzyme Inhibitor Trial in Patients with Chronic Obstructive Pulmonary Disease.
Related Articles

Surprising Results from an Angiotensin-Converting Enzyme Inhibitor Trial in Patients with Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1307-1308

Authors: Ballman KV

PMID: 27905853 [PubMed - in process]




Sweat Chloride: The Critical Biomarker for Cystic Fibrosis Trials.
Related Articles

Sweat Chloride: The Critical Biomarker for Cystic Fibrosis Trials.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1311-1313

Authors: Sontag MK

PMID: 27905852 [PubMed - in process]




Peptide Receptor Radionuclide Therapy for Sarcoidosis.
Related Articles

Peptide Receptor Radionuclide Therapy for Sarcoidosis.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1428-1430

Authors: Lapa C, Grigoleit GU, Hänscheid H, Klinker E, Jung P, Herrmann K, Schirbel A, Böck M, Buck AK, Pelzer T

PMID: 27905851 [PubMed - in process]




Asthma-like Features and Chronic Obstructive Pulmonary Disease.
Related Articles

Asthma-like Features and Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1308-1309

Authors: Hynes G, Pavord ID

PMID: 27905850 [PubMed - in process]




Pathways to Precision Medicine in Idiopathic Pulmonary Fibrosis. Time to Relax?
Related Articles

Pathways to Precision Medicine in Idiopathic Pulmonary Fibrosis. Time to Relax?

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1315-1317

Authors: Hambly N, Kolb M

PMID: 27905849 [PubMed - in process]




Tobacco 21-An Important Public Policy to Protect our Youth.
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Tobacco 21-An Important Public Policy to Protect our Youth.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):P19-P20

Authors:

PMID: 27905848 [PubMed - in process]




Toward Improving Our Understanding of the Link between Mental Health, Lung Function, and Asthma Diagnosis. The Challenge of Asthma Measurement.
Related Articles

Toward Improving Our Understanding of the Link between Mental Health, Lung Function, and Asthma Diagnosis. The Challenge of Asthma Measurement.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1313-1315

Authors: Goodwin RD

PMID: 27905847 [PubMed - in process]




Early Elevation of Plasma Periostin Is Associated with Chronic Ventilator-Dependent Bronchopulmonary Dysplasia.
Related Articles

Early Elevation of Plasma Periostin Is Associated with Chronic Ventilator-Dependent Bronchopulmonary Dysplasia.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1430-1433

Authors: Ahlfeld SK, Davis SD, Kelley KJ, Poindexter BB

PMID: 27905846 [PubMed - in process]




Hospital-acquired Pneumonia: A Host of Factors.
Related Articles

Hospital-acquired Pneumonia: A Host of Factors.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1309-1311

Authors: Sweeney TE, Khatri P

PMID: 27905845 [PubMed - in process]




Deep Phenotyping in Obstructive Sleep Apnea. A Step Closer to Personalized Therapy.
Related Articles

Deep Phenotyping in Obstructive Sleep Apnea. A Step Closer to Personalized Therapy.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1317-1318

Authors: Cistulli PA, Sutherland K

PMID: 27905844 [PubMed - in process]




State of the Heart in Chronic Obstructive Pulmonary Disease: The Best Is Yet to Come.
Related Articles

State of the Heart in Chronic Obstructive Pulmonary Disease: The Best Is Yet to Come.

Am J Respir Crit Care Med. 2016 Dec 1;194(11):1433-1434

Authors: Sotgiu G, Radovanovic D, Santus P

PMID: 27905843 [PubMed - in process]




Genome-wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.
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Genome-wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.

Am J Respir Crit Care Med. 2016 Nov 30;

Authors: Gref A, Kebede Merid S, Gruzieva O, Ballereau S, Becker A, Bellander T, Bergström A, Bossé Y, Bottai M, Chan-Yeung M, Fuertes E, Ierodiakonou D, Jiang R, Joly S, Jones M, Kobor MS, Korek M, Kozyrskyj AL, Kumar A, Lemonnier N, MacIntyre E, Ménard C, Nickle D, Obeidat M, Pellet J, Standl M, Sääf A, Söderhäll C, Tiesler CM, van den Berge M, Vonk JM, Vora H, Xu CJ, Antó JM, Auffray C, Brauer M, Bousquet J, Brunekreef B, Gauderman WJ, Heinrich J, Kere J, Koppelman GH, Postma D, Carlsten C, Pershagen G, Melén E

Abstract
RATIONALE: The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent, and may depend on genetic factors.
OBJECTIVES: To identify gene-environment interaction effects on childhood asthma using genome-wide single nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels.
METHODS: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctor's diagnosis of asthma up to 8 years in three European birth cohorts (n=1,534) with look-up for interaction in two separate North American cohorts, CHS and CAPPS/SAGE (n=1,602 and 186 subjects, respectively). We assessed eQTL effects in human lung specimens and blood, as well as associations between air pollution exposure, methylation and transcriptomic patterns.
MEASUREMENTS AND MAIN RESULTS: In the European cohorts, 186 SNPs had an interaction p-value<1x10(-4) and look-up evaluation of these disclosed eight SNPs in four loci with interaction p<0.05 in the large CHS study, but not in CAPPS/SAGE. Three SNPs within ADCY2 showed same direction of interaction effect, and were found to influence ADCY2 gene expression in peripheral blood (p=4.50x10(-4)). One other SNP with p<0.05 for interaction in CHS, rs686237, strongly influenced B4GALT5 expression in lung tissue (p=1.18x10(-17)). Air pollution exposure was associated with differential DLG2 methylation and expression.
CONCLUSION: Our results indicate that gene-environment interactions are important for asthma development and provide supportive evidence for interaction with air pollution for ADCY2, B4GALT5 and DLG2.

PMID: 27901618 [PubMed - as supplied by publisher]