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351. Morphometric Analysis of Explant Lungs in Cystic Fibrosis.

Author

Boon, Mieke, Verleden, Stijn E., Bosch, Barbara, Lammertyn, Elise J., McDonough, John E., Mai, Cindy, Verschakelen, Johny, Kemner-van de Corput, Mariette, Tiddens, Harm A. W., Proesmans, Marijke, Vermeulen, François L., Verbeken, Erik K., Cooper, Joel, Van Raemdonck, Dirk E., Decramer, Marc, Verleden, Geert M., Hogg, James C., Dupont, Lieven J., Vanaudenaerde, Bart M., and De Boeck, Kris

Abstract

Rationale: After repeated cycles of lung infection and inflammation, patients with cystic fibrosis (CF) evolve to respiratory insufficiency. Although histology and imaging have provided descriptive information, a thorough morphometric analysis of end-stage CF lung disease is lacking.Objectives: To quantify the involvement of small and large airways in end-stage CF.Methods: Multidetector computed tomography (MDCT) and micro-CT were applied to 11 air-inflated CF explanted lungs and 7 control lungs to measure, count, and describe the airway and parenchymal abnormalities in end-stage CF lungs. Selected abnormalities were further investigated with thin section histology.Measurements and Main Results: On MDCT, CF explanted lungs showed an increased median (interquartile range) number (631 [511-710] vs. 344 [277-349]; P = 0.003) and size of visible airways (cumulative airway diameter 217 cm [209-250] vs. 91 cm [80-105]; P < 0.001) compared with controls. Airway obstruction was seen, starting from generation 6 and increasing to 40 to 50% of airways from generation 9 onward. Micro-CT showed that the total number of terminal bronchioles was decreased (2.9/ml [2.6-4.4] vs. 5.3/ml [4.8-5.7]; P < 0.001); 49% were obstructed, and the cross-sectional area of the open terminal bronchioles was reduced (0.093 mm(2) [0.084-0.123] vs. 0.179 mm(2) [0.140-0.196]; P < 0.001). On micro-CT, 41% of the obstructed airways reopened more distally. This remodeling was confirmed on histological analysis. Parenchymal changes were also seen, mostly in a patchy and peribronchiolar distribution.Conclusions: Extensive changes of dilatation and obstruction in nearly all airway generations were observed in end-stage CF lung disease. [ABSTRACT FROM AUTHOR]

Published
2016
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367. Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Author

Ning, Wen, primary, Li, Chao-Jun, additional, Kaminski, Naftali, additional, Feghali-Bostwick, Carol A., additional, Alber, Sean M., additional, Di, Yuanpu P., additional, Otterbein, Sherrie L., additional, Song, Ruiping, additional, Hayashi, Shizu, additional, Zhou, Zhihong, additional, Pinsky, David J., additional, Watkins, Simon C., additional, Pilewski, Joseph M., additional, Sciurba, Frank C., additional, Peters, David G., additional, Hogg, James C., additional, and Choi, Augustine M. K., additional

Published
2004
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376. Radiologic Findings Are Strongly Associated With a Pathologic Diagnosis of Usual Interstitial Pneumonia

Author

Hunninghake, Gary W., primary, Lynch, David A., additional, Galvin, Jeffrey R., additional, Gross, Barry H., additional, Mu¨ller, Nestor, additional, Schwartz, David A., additional, King, Talmadge E., additional, Lynch, Joseph P., additional, Hegele, Richard, additional, Waldron, James, additional, Colby, Thomas V., additional, and Hogg, James C., additional

Published
2003
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381. Circulating hematopoietic progenitor cells in runners

Author

Bonsignore, Maria R., primary, Morici, Giuseppe, additional, Santoro, Alessandra, additional, Pagano, Maria, additional, Cascio, Lucia, additional, Bonanno, Anna, additional, Abate, Pietro, additional, Mirabella, Franco, additional, Profita, Mirella, additional, Insalaco, Giuseppe, additional, Gioia, Maria, additional, Vignola, A. Maurizio, additional, Majolino, Ignazio, additional, Testa, Ugo, additional, and Hogg, James C., additional

Published
2002
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387. The COPD Assessment Test

Author

Gupta, Nisha, Pinto, Lancelot, Benedetti, Andrea, Li, Pei Zhi, Tan, Wan C., Aaron, Shawn D., Chapman, Kenneth R., FitzGerald, J. Mark, Hernandez, Paul, Marciniuk, Darcy D., Maltais, François, O'Donnell, Denis E., Sin, Don, Walker, Brandie L., Bourbeau, Jean, Bourbeau, Jean, Tan, Wan C., FitzGerald, J. Mark, Sin, D.D., Marciniuk, D.D., O'Donnell, D.E., Hernandez, Paul, Chapman, Kenneth R., Cowie, Robert, Aaron, Shawn, Maltais, F., Samet, Jonathon, Puhan, Milo, Hamid, Qutayba, Hogg, James C., Bourbeau, Jean, Baglole, Carole, Jabet, Carole, Mancino, Palmina, Fortier, Yvan, Tan, Wan C., Sin, Don, Tam, Sheena, Road, Jeremy, Comeau, Joe, Png, Adrian, Coxson, Harvey, Kirby, Miranda, Leipsic, Jonathon, Hague, Cameron, Sadatsafavi, Mohsen, To, Teresa, Gershon, Andrea, Tan, Wan C., Coxson, Harvey, Bourbeau, Jean, Li, Pei-Zhi, Duquette, Jean-Francois, Fortier, Yvan, Benedetti, Andrea, Jensen, Denis, O'Donnell, Denis, Tan, Wan C., Lo, Christine, Cheng, Sarah, Fung, Cindy, Haynes, Nancy, Chuang, Junior, Zheng, Liyun, Bourbeau, Jean, Mancino, Palmina, Latreille, David, Baril, Jacinthe, Labonte, Laura, Chapman, Kenneth, McClean, Patricia, Audisho, Nadeen, Cowie, Robert, Cowie, Ann, Dumonceaux, Curtis, Machado, Lisette, Hernandez, Paul, Fulton, Scott, Osterling, Kristen, Aaron, Shawn, Vandemheen, Kathy, Pratt, Gay, Bergeron, Amanda, O'Donnell, Denis, McNeil, Matthew, Whelan, Kate, Maltais, Francois, Brouillard, Cynthia, Marciniuk, Darcy, Clemens, Ron, and Baran, Janet

Abstract

The COPD Assessment Test (CAT) is a valid disease-specific questionnaire measuring health status. However, knowledge concerning its use regarding patient and disease characteristics remains limited. Our main objective was to assess the degree to which the CAT score varies and can discriminate between specific patient population groups.

Published
2016
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391. Loss of GD1-positive Lactobacillus correlates with inflammation in human lungs with COPD.

Author

Sze, Marc A., Utokaparch, Soraya, Elliott, W. Mark, Hogg, James C., and Hegele, Richard G.

Abstract

Objectives: The present study assesses the relationship between contents of GD1 (glycerol dehydratase)-positive Lactobacillus, presence of Lactobacillus and the inflammatory response measured in host lung tissue in mild to moderate chronic obstructive pulmonary disease (COPD). We hypothesise that there will be a loss of GD1 producing Lactobacillus with increasing severity of COPD and that GD1 has anti-inflammatory properties. Setting: Secondary care, 1 participating centre in Vancouver, British Columbia, Canada. Participants: 74 individuals who donated non-cancerous portions of their lungs or lobes removed as treatment for lung cancer (normal lung function controls (n=28), persons with mild (GOLD 1) (n=21) and moderate (GOLD 2) COPD (n=25)). Outcome measures: Primary outcome measure was GD1 positivity within each group and whether or not this impacted quantitative histological measures of lung inflammation. Secondary outcome measures included Lactobacillus presence and quantification, and quantitative histological measurements of inflammation and remodelling in early COPD. Results: Total bacterial count (p>0.05) and prevalence of Lactobacillus (p>0.05) did not differ between groups. However, the GD1 gene was detected more frequently in the controls (14%) than in either mild (5%) or moderate (0%) COPD (p<0.05) samples. Macrophage and neutrophil volume fractions (0.012±0.005 (mean±SD) vs 0.026±0.017 and 0.005±0.002 vs 0.015±0.014, respectively) in peripheral lung tissue were reduced in samples positive for the GD1 gene (p<0.0035). Conclusions: A reduction in GD1 positivity is associated with an increased tissue immune inflammatory response in early stage COPD. There is potential for Lactobacillus to be used as a possible therapeutic, however, validation of these results need to be completed before an anti-inflammatory role of Lactobacillus in COPD can be confirmed. [ABSTRACT FROM AUTHOR]

Published
2015
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392. Genetic regulation of gene expression in the lung identifies CST3 and CD22 as potential causal genes for airflow obstruction.

Author

Lamontagne, Maxime, Timens, Wim, Ke Hao, Bossé, Yohan, Laviolette, Michel, Steiling, Katrina, Campbell, Joshua D., Couture, Christian, Conti, Massimo, Sherwood, Karen, Hogg, James C., Brandsma, Corry-Anke, den Berge, Maarten van, Sandford, Andrew, Lam, Stephen, Lenburg, Marc E., Spira, Avrum, Paré, Peter D., Nickle, David, and Sin, Don D.

Subjects
OBSTRUCTIVE lung diseases, GENETIC regulation, GENE expression, SINGLE nucleotide polymorphisms, PHENOTYPES, CD22 antigen, CELLULAR signal transduction, GENETICS
Abstract

Background COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). Objective To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. Methods We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV1% predicted, FEV1/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. In silico analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. Results High reliability causal relations were found in SNP-mRNA-phenotype triplets for FEV1% predicted (n=169) and FEV1/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (CST3) and CD22 were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease-antiprotease and oxidant-antioxidant balance. Conclusions By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways. [ABSTRACT FROM AUTHOR]

Published
2014
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393. Respiratory Viral Detection and Small Airway Inflammation in Lung Tissue of Patients with Stable, Mild COPD.

Author

Utokaparch, Soraya, Sze, Marc A., Gosselink, John V., McDonough, John E., Elliott, W. Mark, Hogg, James C., and Hegele, Richard G.

Subjects
VIRAL disease diagnosis, AIRWAY (Anatomy), LUNG diseases, NUCLEIC acids, HISTOLOGY, PATIENTS, DISEASES
Abstract

Background: Viral respiratory tract infections are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In lung tissue specimens from patients with stable, mild COPD and from control smokers without airflow obstruction, we determined the prevalence and load of nucleic acid from common respiratory viruses and concomitant inflammation of small airways measuring less than 2-mm in diameter. Methods: Frozen lung tissue obtained from patients with stable, mild COPD ( n = 20) and control subjects ( n = 20) underwent real-time quantitative PCR (qPCR) for 13 respiratory viruses, and quantitative histology for inflammation of small airways. The two groups were compared for viral prevalence and load, and airway inflammation. The relationship between viral load and airway inflammatory cells was also analyzed. Results: Viral nucleic acid were detected in lung tissue of 18/40 (45.0%) of the individuals studied and included seven co-infections that were characterized by a 'dominant virus' contributing to most of the total measured viral load. Lung tissue of COPD patients had a significantly higher prevalence of viral nucleic acid (particularly influenza A virus), and increased inflammation of small airways by macrophages and neutrophils versus controls. In qPCR-positive individuals, linear regression analysis showed a direct correlation between viral load and airway neutrophils, and between influenza A virus load and airway macrophages. Conclusion: The lung tissue of patients with stable, mild COPD has a higher prevalence and load of respiratory viruses versus non-obstructed control subjects, and increased inflammation of small airways. Respiratory viruses may represent potential targets in COPD patient management. [ABSTRACT FROM AUTHOR]

Published
2014
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396. Glucocorticoid-Induced Granulocytosis

Author

Nakagawa, Motohito, primary, Terashima, Takeshi, additional, D’yachkova, Yulia, additional, Bondy, Gregory P., additional, Hogg, James C., additional, and van Eeden, Stephan F., additional

Published
1998
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