Location:
UBC Hospital
work phone: 604-822-7776

Andrew Churg is Professor of Pathology at the University of British Columbia in Vancouver, BC. He obtained his PhD and MD from the University of Chicago, and did a fellowship in lung pathology with Charles Carrington at Stanford University. His laboratory has long focused on the effects of occupational and environmental agents on the lung. In addition he has major interests in the diagnosis of malignant mesothelioma and interstitial lung disease.

For many years he studied the relationship between asbestos fiber burden and disease, and the interactions of exogenous oxidants and particles in the lung. His current basic research efforts are devoted to chronic obstructive lung disease and encompass two areas:

  1. the factors that control small airway remodeling, both that induced by cigarette smoke and that induced by air pollution particles and occupationally encountered dusts;
  2. models of cigarette smoke-induced emphysema in laboratory animals.

In the diagnostic arena, he is the senior author of the 4th Series Fascicle: Tumors of the Serosal Membranes, senior editor of Thurlbeck’s Pathology of the Lung, 3rd Edition, and has published extensively in various areas of diagnostic lung pathology. He is the course director for two CME courses sponsored by the American Society for Clinical Pathology:  Update in Pulmonary Pathology, and Update in Surgical Pathology.

Academic background

  • AB, Columbia University, NY, Chemistry. 1967
  • PhD, University of Chicago, Pathology. 1971
  • MD, University of Chicago, Medicine. 1973
  • Postdoctoral Fellowship, Pulmonary Pathology, Stanford University. 1977-1978
  • Internship and Residency, Pathology, University of Chicago. 1973-1977

Publications

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Well-differentiated Papillary Mesothelioma With Invasive Foci.

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Well-differentiated Papillary Mesothelioma With Invasive Foci.

Am J Surg Pathol. 2014 Mar 10;

Authors: Churg A, Allen T, Borczuk AC, Cagle PT, Galateau-Sallé F, Hwang H, Murer B, Murty VV, Ordonez N, Tazelaar HD, Wick M

Abstract
Well-differentiated papillary mesotheliomas (WDPMs) are usually encountered as incidental findings in the peritoneal cavity in women. Most WDPMs are benign, and the histologic features that indicate a more aggressive course are controversial. We report 20 cases of WDPM, which contained invasive foci. Thirteen cases arose in the peritoneal cavity, 1 in a hernia sac, 3 in the pleural cavity, and 3 in hydroceles. The female:male ratio was 16:4, and age range was 7 to 74 years. Tumor was multifocal in 15 cases. Some tumors showed back-to-back papillae, a pattern mimicking invasion but discernible on pan-keratin stain as compressive crowding. True invasive patterns ranged from simple bland-appearing glands invading the stalks of the papillae to solid foci of invasive tumor of higher cytologic grade than the original WDPM. All 5 tested cases were negative for p16 deletion by fluorescence in situ hybridization, but 2/3 had abnormal karyotypes. Recurrences were seen in 8 patients, and in 4 multiple recurrences were documented. Of 16 patients with follow-up, 14 are alive from periods of 6 months to 6 years (average 3.5 y), and 2 have known recurrent disease. One patient died of disseminated tumor at 8 years but without histologic confirmation of the nature of the tumor. We conclude that WDPM with invasive foci in the papillae appear to be prone to multifocality and recurrence, but that they rarely give rise to life-threatening disease. We suggest that these lesions be called WDPM with invasive foci to alert clinicians to the possibility of recurrence.

PMID: 24618613 [PubMed - as supplied by publisher]

p16 FISH Deletion in Surface Epithelial Mesothelial Proliferations Is Predictive of Underlying Invasive Mesothelioma.

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p16 FISH Deletion in Surface Epithelial Mesothelial Proliferations Is Predictive of Underlying Invasive Mesothelioma.

Am J Surg Pathol. 2014 Feb 5;

Authors: Hwang H, Tse C, Rodriguez S, Gown A, Churg A

Abstract
An atypical mesothelial proliferation along the pleural or peritoneal surface without evidence of invasive tumor poses a diagnostic challenge. Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in mesothelial proliferations, but correlations of p16 status between atypical surface proliferations and underlying mesothelioma have not been described. We used p16 FISH to investigate 11 pleural and 7 peritoneal mesotheliomas that had both an invasive component and a separate surface mesothelial proliferation. In 5/11 pleural samples and 1/7 peritoneal samples, the invasive mesotheliomas showed homozygous deletion of p16 (all cases in excess of 90% of cells deleted); the surface proliferation in all 6 cases with deletion in the invasive tumor was also p16 deleted. Conversely, the 12 tumors that did not show p16 deletion in the invasive compartment also did not have deletion in the surface component. We conclude that (1) surface mesothelial proliferations near invasive mesotheliomas show the same pattern of p16 by FISH as the underlying tumor and may represent in situ disease or growth of the underlying mesothelioma along the serosal surface; (2) p16 deletion in mesothelial surface proliferations is strongly associated with p16 deletion in underlying mesotheliomas, and biopsies consisting of pure surface mesothelial proliferations that are p16 deleted allow a diagnosis of mesothelioma without an additional biopsy if there is clinical (thoracosopic/laparoscopic) or radiologic evidence of diffuse pleural or peritoneal tumor; (3) however, the absence of p16 deletion in surface proliferations does not rule out underlying invasive mesothelioma.

PMID: 24503757 [PubMed - as supplied by publisher]

Club cell protein 16 and disease progression in chronic obstructive pulmonary disease.

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Club cell protein 16 and disease progression in chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 2013 Dec 15;188(12):1413-9

Authors: Park HY, Churg A, Wright JL, Li Y, Tam S, Man SF, Tashkin D, Wise RA, Connett JE, Sin DD

Abstract
RATIONALE: Club (Clara) cell protein 16 (CC-16) is a protein that is synthesized predominantly in the lungs and is detectable in serum. Its expression decreases with lung injury and smoking, and is thus a marker of bronchial cell dysfunction.
OBJECTIVES: To evaluate the possibility of using serum CC-16 as a biomarker for disease progression in chronic obstructive pulmonary disease (COPD).
METHODS: We measured serum CC-16 levels from 4,724 subjects with mild-to-moderate airflow limitation in the Lung Health Study. Using a linear regression model, we determined the relationship of serum CC-16 concentrations to decline in lung function over 9 years. In addition, to determine whether CC-16 plays a major role in the pathogenesis of mild COPD, we exposed CC-16-deficient (-/-) mice to 6 months of cigarette smoke.
MEASUREMENTS AND MAIN RESULTS: Reduced serum concentrations of CC-16 were associated with accelerated decline in FEV1 over 9 years (P < 0.0001), and this association persisted after adjustments for age, sex, race, smoking status, airway reactivity, body mass index, and baseline FEV1 (P = 0.0002). However, CC-16(-/-) mice did not demonstrate an enhanced risk of emphysema or small airway remodeling in response to cigarette smoke.
CONCLUSIONS: Serum CC-16 is associated with disease progression, and may assist in the identification of "rapid progressors." However, the absence of CC-16 does not appear to modify the risk of cigarette-related COPD in mice.

PMID: 24245748 [PubMed - indexed for MEDLINE]

Respiratory bronchiolitis with fibrosis. High-resolution computed tomography findings and correlation with pathology.

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Respiratory bronchiolitis with fibrosis. High-resolution computed tomography findings and correlation with pathology.

Ann Am Thorac Soc. 2013 Dec;10(6):590-601

Authors: Reddy TL, Mayo J, Churg A

Abstract
BACKGROUND: Recent pathology studies report that the lungs of cigarette smokers may demonstrate small localized subpleural foci of interstitial fibrosis associated with emphysema. Pathologically, this lesion has been termed smoking-related interstitial fibrosis, respiratory bronchiolitis-interstitial lung disease (ILD) with fibrosis, or airspace enlargement with fibrosis, but it is commonly misinterpreted on imaging and biopsy as a diffuse fibrosing interstitial pneumonia. The high-resolution computed tomography (HRCT) appearance of this process has not been defined.
OBJECTIVES: We describe HRCT imaging of seven patients with this lesion present histologically.
MEASUREMENTS AND MAIN RESULTS: HRCT features consisted of patchy areas of mild reticulation around predominantly subpleural upper/mid zone emphysematous changes in all cases, with variable patchy ground-glass change in six cases. Pathologically, there were distinctly circumscribed foci of dense, often hyalinized, interstitial fibrosis mixed with emphysema; variable numbers of smoker's macrophages were present in the airspaces. The fibrosis was confined to the subpleural regions. Three patients with follow-up information were clinically stable.
CONCLUSIONS: These data suggest that a CT pattern of patchy areas of reticular changes about predominantly upper zone emphysematous spaces may be seen in smokers who do not have clinical evidence of a diffuse ILD. We propose that this lesion be called respiratory bronchiolitis with fibrosis (RBF) to avoid confusion with other forms of ILD. RBF probably accounts for some of the cases of ILD seen in large radiologic surveys of smokers. The pathology literature indicates that RBF either has no functional effects or at worst represents mild, usually nonprogressive disease, and hence separation from other, more serious, forms of ILD is important. Recognition of this lesion on imaging may obviate the need for lung biopsy.

PMID: 24024643 [PubMed - in process]

Aging does not enhance experimental cigarette smoke-induced COPD in the mouse.

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Aging does not enhance experimental cigarette smoke-induced COPD in the mouse.

PLoS One. 2013;8(8):e71410

Authors: Zhou S, Wright JL, Liu J, Sin DD, Churg A

Abstract
It has been proposed that the development of COPD is driven by premature aging/premature senescence of lung parenchyma cells. There are data suggesting that old mice develop a greater inflammatory and lower anti-oxidant response after cigarette smoke compared to young mice, but whether these differences actually translate into greater levels of disease is unknown. We exposed C57Bl/6 female mice to daily cigarette smoke for 6 months starting at age 3 months (Ayoung@) or age 12 months (Aold@), with air-exposed controls. There were no differences in measures of airspace size between the two control groups and cigarette smoke induced exactly the same amount of emphysema in young and old. The severity of smoke-induced small airway remodeling using various measures was identical in both groups. Smoke increased numbers of tissue macrophages and neutrophils and levels of 8-hydroxyguanosine, a marker of oxidant damage, but there were no differences between young and old. Gene expression studies using laser capture microdissected airways and parenchyma overall showed a trend to lower levels in older animals and a somewhat lesser response to cigarette smoke in both airways and parenchyma but the differences were usually not marked. Telomere length was greatest in young control mice and was decreased by both smoking and age. The senescence marker p21(Waf1) was equally upregulated by smoke in young and old, but p16(INK4a), another senescence marker, was not upregulated at all. We conclude, in this model, animal age does not affect the development of emphysema and small airway remodeling.

PMID: 23936505 [PubMed - in process]

Data set for reporting of lung carcinomas: recommendations from International Collaboration on Cancer Reporting.

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Data set for reporting of lung carcinomas: recommendations from International Collaboration on Cancer Reporting.

Arch Pathol Lab Med. 2013 Aug;137(8):1054-62

Authors: Jones KD, Churg A, Henderson DW, Hwang DM, Wyatt JM, Nicholson AG, Rice AJ, Washington MK, Butnor KJ

Abstract
CONTEXT: The International Collaboration on Cancer Reporting (ICCR) is a quadripartite alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, and the Canadian Partnership Against Cancer. The ICCR was formed with a view to reducing the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish, and maintain standardized cancer-reporting data sets. The resultant standardization of cancer reporting would be expected to benefit not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets.
OBJECTIVES: To develop an evidence-based reporting data set for each cancer site.
DESIGN: A project to develop data sets for prostate, endometrium, and lung cancers and malignant melanoma was piloted by the quadripartite group.
RESULTS: A set of required and recommended data elements and appropriate responses for each element were agreed upon for the reporting of lung cancer.
CONCLUSIONS: This review describes the process of development of the lung cancer data set.

PMID: 23899061 [PubMed - indexed for MEDLINE]

IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations.

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IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations.

Am J Surg Pathol. 2013 Mar;37(3):421-6

Authors: Lee AF, Gown AM, Churg A

Abstract
Distinguishing malignant mesotheliomas from benign mesothelial proliferations on hematoxylin and eosin-stained sections can be extremely challenging. Various immunohistochemical stains have been suggested to help in making this distinction, but all are controversial. Recently, IMP3 (insulin-like growth factor II mRNA binding protein 3) and GLUT-1 (glucose transporter protein 1) have been proposed as immunohistochemical markers that are positive in mesotheliomas but not in benign proliferations. We evaluated the performance of these markers on a tissue microarray containing 30 malignant mesotheliomas and 48 benign thoracic or abdominal mesothelial proliferations. IMP3 was positive in 53% of malignant and 27% of benign cases (P=0.03), whereas GLUT-1 was positive in 60% of malignant and 13% of benign cases (P=0.0003). Forty-three percent of malignant cases, but only 4% of benign cases, were positive for both IMP3 and GLUT-1 (P=0.00003). We conclude that, statistically, both IMP3 and GLUT-1 are more frequently positive in malignant compared with benign mesothelial processes; however, the frequency of positive staining in benign cases is too high to allow their diagnostic use as single stains. The combination of both markers may be of greater diagnostic value, but this hypothesis should be confirmed in further studies.

PMID: 23108021 [PubMed - indexed for MEDLINE]

The separation of benign and malignant mesothelial proliferations.

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The separation of benign and malignant mesothelial proliferations.

Arch Pathol Lab Med. 2012 Oct;136(10):1217-26

Authors: Churg A, Galateau-Salle F

Abstract
CONTEXT: The separation of benign from malignant mesothelial proliferations is crucial to patient management but is often a difficult problem for the pathologist.
OBJECTIVE: To review the pathologic features that allow separation of benign from malignant mesothelioma proliferations, with an emphasis on new findings.
DATA SOURCES: Literature review and experience of the authors.
CONCLUSIONS: Invasion is still the most reliable indicator of malignancy. The distribution and amount of proliferating mesothelial cells are important in separating benignity from malignancy, and keratin stains can be valuable because they highlight the distribution of mesothelial cells. Hematoxylin-eosin examination remains the gold standard, and the role of immunochemistry is extremely controversial; we believe that at present there is no reliable immunohistochemical marker of malignancy in this setting. Mesothelioma in situ is a diagnosis that currently cannot be accurately made by any type of histologic examination. Desmoplastic mesotheliomas are characterized by downward growth of keratin-positive spindled cells between S100-positive fat cells; some cases of organizing pleuritis can mimic involvement of fat, but these fat-like spaces are really S100-negative artifacts aligned parallel to the pleural surface. Fluorescence in situ hybridization on tissue sections to look for homozygous p16 gene deletions is occasionally useful, but many mesotheliomas do not show homozygous p16 deletions. Equivocal biopsy specimens should be diagnosed as atypical mesothelial hyperplasia and another biopsy requested if the clinicians believe the process is malignant.

PMID: 23020727 [PubMed - indexed for MEDLINE]

Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice.

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Utility of a CEA, CD15, calretinin, and CK5/6 panel for distinguishing between mesotheliomas and pulmonary adenocarcinomas in clinical practice.

Am J Surg Pathol. 2012 Oct;36(10):1503-8

Authors: Mohammad T, Garratt J, Torlakovic E, Gilks B, Churg A

Abstract
Most reports on antibodies that claimed to separate mesothelioma from pulmonary adenocarcinoma originated from academic centers or specialized immunohistochemistry laboratories, but little is known about how such stains perform in general practice laboratories. The Canadian Immunohistochemistry Quality Control program circulates tissue array slides to laboratories across Canada; these are stained and then interpreted by the local laboratory and by a set of experienced reviewers. For Canadian Immunohistochemistry Quality Control run 16, tissue array slides from 16 pulmonary adenocarcinomas and 6 mesotheliomas were stained in 36 different laboratories for CEA, CD15, CK5/6, and calretinin. A total of 736 results (cores) were interpretable. If 3 of 4 staining results concordant with the diagnosis was accepted as definitive, 166/192 (86.4%) mesothelioma cores and 461/544 (84.7%) adenocarcinoma cores were correctly diagnosed. However, if 4 of 4 concordant markers were required, then 93/192 (48.4%) mesothelioma cores and 265/544 (48.7%) adenocarcinoma cores were correctly diagnosed. Only 3/192 (1.6%) mesothelioma cores were incorrectly classified as carcinomas and 8/544 (1.5%) of adenocarcinoma cores incorrectly classified as mesotheliomas on the basis of the immunoprofile (ie, 3 of 4 or 4 of 4 marker results were discordant with the diagnosis). We conclude that, in a study based on results from nonspecialized laboratories, the combination of CEA, CD15, calretinin, and CK5/6, used as a panel, has a very low false-positive rate when separating pulmonary adenocarcinomas from mesotheliomas; however, single negative or incorrect results are common, therefore the panel is only useful diagnostically if 3 of 4 correct results are deemed acceptable for diagnosis.

PMID: 22982894 [PubMed - indexed for MEDLINE]

Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group.

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Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group.

Arch Pathol Lab Med. 2013 May;137(5):647-67

Authors: Husain AN, Colby T, Ordonez N, Krausz T, Attanoos R, Beasley MB, Borczuk AC, Butnor K, Cagle PT, Chirieac LR, Churg A, Dacic S, Fraire A, Galateau-Salle F, Gibbs A, Gown A, Hammar S, Litzky L, Marchevsky AM, Nicholson AG, Roggli V, Travis WD, Wick M, International Mesothelioma Interest Group

Abstract
CONTEXT: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.
OBJECTIVE: To provide updated practical guidelines for the pathologic diagnosis of MM.
DATA SOURCES: Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks.
CONCLUSIONS: There was consensus opinion regarding (1) distinction of benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiation of epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. It is recommended that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

PMID: 22929121 [PubMed - indexed for MEDLINE]

Regional heterogeneity in murine lung fibroblasts from normal mice or mice exposed once to cigarette smoke.

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Regional heterogeneity in murine lung fibroblasts from normal mice or mice exposed once to cigarette smoke.

PLoS One. 2012;7(6):e39761

Authors: Preobrazhenska O, Wright JL, Churg A

Abstract
Chronic obstructive lung disease (COPD) is characterized by matrix deposition in the small airways but matrix loss from the parenchyma, phenomena which must depend on the ability of local fibroblasts to produce matrix after smoke exposure. To investigate this idea, we exposed C57Bl/6 mice once to cigarette smoke or to air (control) and prepared primary cultures of lung fibroblasts by microdissecting large airways (trachea, LAF), medium size airways (major bronchi, MAF) and parenchyma (PF). Control PF showed the lowest rate of wound closure and wound closure was depressed in all lines by a single in vivo smoke exposure. Gene expression of matrix proteins differed considerably among the sites; decorin, which may sequester TGFβ, was markedly higher in PF. PF showed higher intrinsic ratios of pSmad2/Smad2. Smoke caused much greater increases in secreted and matrix deposited collagens 1 and 3 in PF than in LAF or MAF. Expression of Thy-1, a gene that suppresses myofibroblast differentiation, was increased by smoke in PF. We conclude that there is considerable regional heterogeneity in murine lung fibroblasts in terms of matrix production, either basally or after in vivo smoke exposure; that PF have lower ability to repair wounds and higher intrinsic TGFβ signaling; and that a single exposure to smoke produces lasting changes in the pattern of matrix production and wound repair, changes that may be mediated in part by smoke-induced release of TGFβ. However, PF still retain the ability to repair by producing new matrix after a single in vivo smoke exposure.

PMID: 22761892 [PubMed - indexed for MEDLINE]

Pulmonary alveolar proteinosis as a reaction to fentanyl patch smoke.

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Pulmonary alveolar proteinosis as a reaction to fentanyl patch smoke.

Chest. 2012 May;141(5):1321-3

Authors: Chapman E, Leipsic J, Satkunam N, Churg A

Abstract
We report a patient who developed shortness of breath and systemic symptoms after starting to smoke fentanyl patches. CT scan showed ground glass centrilobular nodules, and biopsy demonstrated alveolar proteinosis. Her symptoms disappeared and her chest imaging changes largely resolved when she stopped smoking the patches. Alveolar proteinosis is an uncommon drug reaction and in this case presented in a very unusual fashion as an inhalation injury.

PMID: 22553265 [PubMed - indexed for MEDLINE]

Pulmonary hyalinizing granuloma with associated elevation in serum and tissue IgG4 occurring in a patient with a history of sarcoidosis.

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Pulmonary hyalinizing granuloma with associated elevation in serum and tissue IgG4 occurring in a patient with a history of sarcoidosis.

Am J Surg Pathol. 2012 May;36(5):774-8

Authors: Chapman EM, Gown A, Mazziotta R, Churg A

Abstract
Pulmonary hyalinizing granulomas (PHGs) are unusual fibrosclerotic inflammatory lung lesions. The organ-based manifestations of the recently defined IgG4-related sclerosing disease typically show dense fibrosis and heavy lymphoplasmacytic infiltrates. IgG4-related sclerosing disease is also defined by increased serum IgG4 levels and increased tissue levels of IgG4-positive plasma cells. The morphologic features of PHG overlap with those seen in IgG4-related sclerosing disease, and this suggests that PHG may be a form of IgG4-related sclerosing disease. We present a case of a 51-year-old man with a history of sarcoidosis who presented with slowly enlarging pulmonary nodules. Histologic evaluation of one of the nodules yielded a diagnosis of PHG. Further investigation demonstrated both elevated serum IgG4 and elevated tissue IgG4-positive plasma cells in the PHG. In previous reports, lesions that are now considered part of IgG4-related sclerosing disease were documented in patients also diagnosed with PHG, although these reports date from before the description of IgG4 sclerosing disease. This case provides the first definitive evidence that PHG is part of the spectrum of IgG4-related sclerosing disease.

PMID: 22498827 [PubMed - indexed for MEDLINE]

The complex relationship of serum adiponectin to COPD outcomes COPD and adiponectin.

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The complex relationship of serum adiponectin to COPD outcomes COPD and adiponectin.

Chest. 2012 Oct;142(4):893-99

Authors: Yoon HI, Li Y, Man SF, Tashkin D, Wise RA, Connett JE, Anthonisen NA, Churg A, Wright JL, Sin DD

Abstract
BACKGROUND: COPD is a chronic inflammatory disorder with high risk of cardiovascular morbidity and mortality. Adiponectin is a hormone that has anti inflammatory, antidiabetic, and anti atherogenic activities. We investigated the relationship of serum adiponectin to health outcomes in COPD.
METHODS: We measured adiponectin levels in serum samples from participants of the Lung Health Study, who were smokers with mild to moderate airflow limitation. We determined the relationship of serum adiponectin to hospitalization and mortality using a Cox proportional hazards model and to baseline lung function measurements and bronchial reactivity using multiple regression methods.
RESULTS: Serum adiponectin concentrations were inversely related to hospitalizations and mortality from coronary heart disease (hazard ratio [HR], 0.73; 95% CI, 0.62-0.86) and to cardiovascular disease (HR, 0.83; 95% CI, 0.73-0.94) and positively related to deaths from respiratory causes (HR, 2.09; 95% CI, 1.41-3.11). However, serum adiponectin concentrations were not significantly related to total mortality (HR, 1.10; 95% CI, 0.93-1.29) or cancer-related mortality(HR, 1.11; 95% CI, 0.92-1.34). Serum adiponectin concentrations were significantly related to increased bronchial reactivity and an accelerated decline in lung function (both P , .0001). Smoking status had no material influence on serum adiponectin concentrations.
CONCLUSIONS: Adiponectin is a complex serum biomarker in COPD that is associated with decreased risk of cardiovascular events but increased risk of respiratory mortality. Because serum adiponectin is not significantly influenced by smoking status, it is a very promising biomarker of cardiovascular outcomes in COPD.

PMID: 22207678 [PubMed - indexed for MEDLINE]

Late intervention with a myeloperoxidase inhibitor stops progression of experimental chronic obstructive pulmonary disease.

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Late intervention with a myeloperoxidase inhibitor stops progression of experimental chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 2012 Jan 1;185(1):34-43

Authors: Churg A, Marshall CV, Sin DD, Bolton S, Zhou S, Thain K, Cadogan EB, Maltby J, Soars MG, Mallinder PR, Wright JL

Abstract
RATIONALE: Inflammation and oxidative stress are linked to the deleterious effects of cigarette smoke in producing chronic obstructive pulmonary disease (COPD). Myeloperoxidase (MPO), a neutrophil and macrophage product, is important in bacterial killing, but also drives inflammatory reactions and tissue oxidation.
OBJECTIVES: To determine the role of MPO in COPD.
METHODS: We treated guinea pigs with a 2-thioxanthine MPO inhibitor, AZ1, in a 6-month cigarette smoke exposure model, with one group receiving compound from Smoking Day 1 and another group treated after 3 months of smoke exposure.
RESULTS: At 6 months both treatments abolished smoke-induced increases in lavage inflammatory cells, largely ameliorated physiological changes, and prevented or stopped progression of morphologic emphysema and small airway remodeling. Cigarette smoke caused a marked increase in immunohistochemical staining for the myeloperoxidase-generated protein oxidation marker dityrosine, and this effect was considerably decreased with both treatment arms. Serum 8-isoprostane, another marker of oxidative stress, showed similar trends. Both treatments also prevented muscularization of the small intrapulmonary arteries, but only partially ameliorated smoke-induced pulmonary hypertension. Acutely, AZ1 prevented smoke-induced increases in expression of cytokine mediators and nuclear factor-κB binding.
CONCLUSIONS: We conclude that an MPO inhibitor is able to stop progression of emphysema and small airway remodeling and to partially protect against pulmonary hypertension, even when treatment starts relatively late in the course of long-term smoke exposure, suggesting that inhibition of MPO may be a novel and useful therapeutic treatment for COPD. Protection appears to relate to inhibition of oxidative damage and down-regulation of the smoke-induced inflammatory response.

PMID: 21997333 [PubMed - indexed for MEDLINE]

Research Interest

  • Pathology of occupational lung disease: diagnosis and mechanisms
  • Cardiovascular & Pulmonary disease