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Igor Z Barjaktarevic,1 Russell G Buhr,1,2 Xiaoyan Wang,3 Scott Hu,1 David Couper,4 Wayne Anderson,4 Richard E Kanner,5 Robert Paine III,5 Surya P Bhatt,6 Nirav R Bhakta,7 Mehrdad Arjomandi,7 Robert J Kaner,8 Cheryl S Pirozzi,5 Jeffrey L Curtis,9,10 Wanda K O’Neal,4 Prescott G Woodruff,7 MeiLan K Han,9 Fernando J Martinez,8 Nadia Hansel,11 James Michael Wells,6 Victor E Ortega,12 Eric A Hoffman,13 Claire M Doerschuk,4 Victor Kim,14 Mark T Dransfield,6 M Bradley Drummond,4 Russell Bowler,15 Gerard Criner,14 Stephanie A Christenson,7 Bonnie Ronish,5 Stephen P Peters,12 Jerry A Krishnan,16 Donald P Tashkin,1 Christopher B Cooper1 On behalf of the NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS)1Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; 2Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA; 3Department of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, CA, USA; 4Department of Medicine, University of North Carolina, Chapel Hill, NC, USA; 5Department of Medicine, University of Utah, Salt Lake City, UT, USA; 6Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 7Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; 8Department of Medicine, Weill Cornell Weill Cornell Medical Center, New York, NY, USA; 9Department of Medicine, University of Michigan, Ann Arbor, MI, USA; 10Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; 11Department of Medicine, John Hopkins University, Baltimore, MD, USA; 12Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 13Department of Medicine, University of Iowa, Iowa City, IA, USA; 14Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; 15Department of Medicine, National Jewish Health Systems, Denver, CO, USA; 16Department of Medicine, University of Illinois at Chicago, Chicago, IL, USACorrespondence: Christopher B CooperDepartments of Medicine and Physiology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, 37-131 CHS, Los Angeles, CA 90095, USAEmail ccooper@mednet.ucla.eduObjective: Bronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV1 (BDRFEV1) as a measure reflecting the change in flow and in FVC (BDRFVC) reflecting the change in volume.Methods: We analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.Results: A majority of COPD participants exhibited BDR (52.7%). BDRFEV1 occurred more often in earlier stages of COPD, while BDRFVC occurred more frequently in more advanced disease. When defined by increases in either FEV1 or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDRFVC was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDRFVC was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV1.Conclusion: With advanced airflow obstruction in COPD, BDRFVC is more prevalent in comparison to BDRFEV1 and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV1, BDRFVC itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.Clinical trials registration: ClinicalTrials.gov: NCT01969344T4.Keywords: bronchodilator responsiveness, inspiratory capacity, FVC, FEV1, SPIROMICS

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10-8) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.© 2014 Nature America, Inc. All rights reserved.

Barjaktarevic IZ, Buhr RG, Wang X, et al. Int J Chron Obstruct Pulmon Dis. 2019;14:2927– 2938. The authors have advised that there is an error in the Funding section on page 2935. The correct funding statement is as follows: FundingThis study was supported by R01HL125432-01A1 (MBD), T32HL007106-41 (RMB), and TL1TR001883-01 (RGB). SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN268200900013C, HHSN2682009 00014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200 900019C, and HHSN268200900020C) and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune, Bayer, Bellerophon Therapeutics, Boehringer-Ingelheim Pharmaceuticals, Inc., Chiesi Farmaceutici S.p.A., Forest Research Institute, Inc., GlaxoSmithKline, Grifols Therapeutics, Inc., Ikaria, Inc., Nycomed GmbH, Takeda Pharmaceutical Company, Novartis Pharmaceuticals Corporation, ProterixBio; Regeneron Pharmaceuticals, Inc., Sanofi, and Sunovion. The PRM analyses were supported by NHLBI HL122438 and HL138188. Mehrdad Arjomandi was supported by a grant from the Flight Attendant Medical Research Institute. The authors apologize for this error. Read the original article

Indoor air pollution has been linked to adverse chronic obstructive pulmonary disease ( COPD) health, but specific causative agents have not yet been identified. We evaluated the role of indoor endotoxin exposure upon respiratory health in former smokers with COPD. Eighty-four adults with moderate to severe COPD were followed longitudinally and indoor air and dust samples collected at baseline, 3 and 6 months. Respiratory outcomes were repeatedly assessed at each time point. The associations between endotoxin exposure in air and settled dust and health outcomes were explored using generalizing estimating equations in multivariate models accounting for confounders. Dust endotoxin concentrations in the main living area were highest in spring and lowest in fall, while airborne endotoxins remained steady across seasons. Airborne and dust endotoxin concentrations were weakly correlated with one another ( r s = +0.24, P = 0.005). Endotoxin concentrations were not significantly associated with respiratory symptoms, rescue medication use, quality of life, or severe exacerbations. In vitro whole-blood assays of the pro-inflammatory capacity of PM10 filters with and without endotoxin depletion demonstrated that the endotoxin component of indoor air pollution was not the primary trigger for interleukin-1 β release. Our findings support that endotoxin is not the major driver in the adverse effects of indoor PM upon COPD morbidity. [ABSTRACT FROM AUTHOR]