Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers

Respiratory Research

Carl Magnus Sköld²  Sven Nyrén¹  Åsa M Wheelock²  Mikael Mikko²  Helena Forsslund²  Göran Tornling²  Reza Karimi² 

[1] Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;Department of Medicine and Center for Molecular Medicine (CMM), Karolinska Institutet, Lung-Allergy Clinic N2:02, Karolinska University Hospital Solna, Stockholm, SE 171 76, Sweden

关键词: Bronchoalveolar lavage;    Gender;    Lung function;    CT;    Smoking;    Lung density;    Attenuation;    Inflammation;   

Others  :  790393
DOI  :  10.1186/1465-9921-15-23

 received in 2013-10-21, accepted in 2014-02-16,  发布年份 2014

【 摘 要 】

Background

Smokers have increased cell concentration in the lower respiratory tract indicating a chronic inflammatory state, which in some individuals may lead to development of chronic obstructive pulmonary disease (COPD). Computer tomography (CT) imaging provides means of quantifying pulmonary structure and early signs of disease. We investigated whether lung density on high resolution CT differs between smokers and never-smokers and if this were associated to intensity of inflammation.

Methods

Forty smoking volunteers with normal pulmonary function, 40 healthy never-smokers and 40 patients with COPD of GOLD stage I-II, were included. Mean lung attenuation and percentage of pixels in the lung with attenuation between −750 and −900 HU (percentage higher density spectrum (%HDS)) were calculated on inspiratory CT-scans. Markers of systemic inflammation in blood and cell counts in bronchoalveolar lavage (BAL) fluid were recorded.

Results

Lung density expressed as %HDS was increased in smokers (44.0 ± 5.8%) compared to both never-smokers (38.3 ± 5.8%) and patients with COPD (39.1 ± 5.8%), (p < 0.001, for both). Females had denser lungs than males, which was dependent on body height. Cell concentration in BAL were correlated to lung density in smokers (r = 0.50, p < 0.001).

Conclusions

Lung density on CT is associated with cell concentration in BAL in smokers and may mirror an inflammatory response in the lung. Gender difference in lung density is dependent on height. In COPD with emphysema, loss of lung tissue may counterbalance the expected increase in density due to inflammation. The findings may help to interpret high resolution CT in the context of smoking and gender and highlight the heterogeneity of structural changes in COPD.

【 授权许可】

   
2014 Karimi et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Fraig M, Shreesha U, Savici D, Katzenstein AL: Respiratory bronchiolitis: a clinicopathologic study in current smokers, ex-smokers, and never-smokers. Am J Surg Pathol 2002, 26:647-653.
• [2]Engstrom G, Segelstorm N, Ekberg-Aronsson M, Nilsson PM, Lindgarde F, Lofdahl CG: Plasma markers of inflammation and incidence of hospitalisations for COPD: results from a population-based cohort study. Thorax 2009, 64:211-215.
• [3]Morrison D, Rahman I, Lannan S, MacNee W: Epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers. Am J Respir Crit Care Med 1999, 159:473-479.
• [4]Chong D, Brown MS, Kim HJ, van Rikxoort EM, Guzman L, McNitt-Gray MF, Khatonabadi M, Galperin-Aizenberg M, Coy H, Yang K, Goldin JG: Reproducibility of volume and densitometric measures of emphysema on repeat computed tomography with an interval of 1 week. Eur Radiol 2012, 22:287-294.
• [5]Coxson HO, Mayo JR, Behzad H, Moore BJ, Verburgt LM, Staples CA, Pare PD, Hogg JC: Measurement of lung expansion with computed tomography and comparison with quantitative histology. J Appl Physiol 1995, 79:1525-1530.
• [6]Gevenois PA, de Maertelaer V, De Vuyst P, Zanen J, Yernault JC: Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med 1995, 152:653-657.
• [7]Mohamed Hoesein FA, Schmidt M, Mets OM, Gietema HA, Lammers JW, Zanen P, de Koning HJ, van der Aalst C, Oudkerk M, Vliegenthart R, Isqum L, Prokop M, Van Ginneken B, Van Rikxoort EM, de Jong PA: Discriminating dominant computed tomography phenotypes in smokers without or with mild COPD. Respir Med 2014, 108(1):136-143.
• [8]Remy-Jardin M, Remy J, Boulenguez C, Sobaszek A, Edme JL, Furon D: Morphologic effects of cigarette smoking on airways and pulmonary parenchyma in healthy adult volunteers: CT evaluation and correlation with pulmonary function tests. Radiology 1993, 186:107-115.
• [9]Mohamed Hoesein FA, de Jong PA, Lammers JW, Mali WP, Schmidt M, de Koning HJ, van der Aalst C, Oudkerk M, Vliegenthart R, van Ginneken B, van Rikxoort EM, Zanen P: Computed tomography structural lung changes in discordant airflow limitation. PloS one 2013, 8:e65177.
• [10]Gierada DS, Yusen RD, Pilgram TK, Crouch L, Slone RM, Bae KT, Lefrak SS, Cooper JD: Repeatability of quantitative CT indexes of emphysema in patients evaluated for lung volume reduction surgery. Radiology 2001, 220:448-454.
• [11]Newell JD Jr, Hogg JC, Snider GL: Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema. Eur Respir J 2004, 23:769-775.
• [12]Shaker SB, Dirksen A, Lo P, Skovgaard LT, de Bruijne M, Pedersen JH: Factors influencing decline in lung density in a Danish lung cancer screening cohort. Eur Respir J 2012.
• [13]Kohler M, Sandberg A, Kjellqvist S, Thomas A, Karimi R, Nyren S, Eklund A, Thevis M, Skold CM, Wheelock AM: Gender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol 2013, 131:743-751.
• [14]Forsslund H, Mikko M, Karimi R, Grunewald J, Wheelock AM, Wahlstrom J, Skold CM: Distribution of T cell subsets in bronchoalveolar lavage fluid of patients with mild to moderate COPD is dependent on current smoking status and not airway obstruction. Chest 2013, 21:13-0873.
• [15]Cotes JE, Chinn DJ, Quanjer PH, Roca J, Yernault JC: Standardization of the measurement of transfer factor (diffusing capacity). report working party standardization of lung function tests, european community for steel and coal. Official statement of the european respiratory society. Eur Respir J Suppl 1993, 16:41-52.
• [16]Adesina AM, Vallyathan V, McQuillen EN, Weaver SO, Craighead JE: Bronchiolar inflammation and fibrosis associated with smoking. A morphologic cross-sectional population analysis. Am Rev Respir Dis 1991, 143:144-149.
• [17]Dirksen A, Friis M, Olesen KP, Skovgaard LT, Sorensen K: Progress of emphysema in severe alpha 1-antitrypsin deficiency as assessed by annual CT. Acta Radiol 1997, 38:826-832.
• [18]Muller NL, Staples CA, Miller RR, Abboud RT: “Density mask”. An objective method to quantitate emphysema using computed tomography. Chest 1988, 94:782-787.
• [19]Gould GA, MacNee W, McLean A, Warren PM, Redpath A, Best JJ, Lamb D, Flenley DC: CT measurements of lung density in life can quantitate distal airspace enlargement–an essential defining feature of human emphysema. Am Rev Respir Dis 1988, 137:380-392.
• [20]Karimi R, Tornling G, Grunewald J, Eklund A, Skold CM: Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history. PloS one 2012, 7:e34232.
• [21]de Oca MM, Halbert RJ, Lopez MV, Perez-Padilla R, Talamo C, Moreno D, Muino A, Jardim JR, Valdivia G, Pertuze J, Menezes AM: The chronic bronchitis phenotype in subjects with and without COPD: the PLATINO study. Eur Respir J 2012, 40:28-36.
• [22]Willems LN, Kramps JA, Stijnen T, Sterk PJ, Weening JJ, Dijkman JH: Relation between small airways disease and parenchymal destruction in surgical lung specimens. Thorax 1990, 45:89-94.
• [23]Remy-Jardin M, Edme JL, Boulenguez C, Remy J, Mastora I, Sobaszek A: Longitudinal follow-up study of smoker’s lung with thin-section CT in correlation with pulmonary function tests. Radiology 2002, 222:261-270.
• [24]Lederer DJ, Enright PL, Kawut SM, Hoffman EA, Hunninghake G, van Beek EJ, Austin JH, Jiang R, Lovasi GS, Barr RG: Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study. Am J Respir Crit Care Med 2009, 180:407-414.
• [25]Soejima K, Yamaguchi K, Kohda E, Takeshita K, Ito Y, Mastubara H, Oguma T, Inoue T, Okubo Y, Amakawa K, Tateno H, Shiomi T: Longitudinal follow-up study of smoking-induced lung density changes by high-resolution computed tomography. Am J Respir Crit Care Med 2000, 161:1264-1273.
• [26]Ashraf H, Lo P, Shaker SB, de Bruijne M, Dirksen A, Tonnesen P, Dahlback M, Pedersen JH: Short-term effect of changes in smoking behaviour on emphysema quantification by CT. Thorax 2011, 66:55-60.
• [27]Kuschner WG, D’Alessandro A, Wong H, Blanc PD: Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J 1996, 9:1989-1994.
• [28]Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis, and selected comparison groups. The BAL Cooperative Group Steering Committee Am Rev Respir Dis 1990, 141:S169-202.
• [29]Thomsen M, Dahl M, Lange P, Vestbo J, Nordestgaard BG: Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012, 186(10):982-829.
• [30]Moszczynski P, Zabinski Z, Moszczynski P Jr, Rutowski J, Slowinski S, Tabarowski Z: Immunological findings in cigarette smokers. Toxicol Lett 2001, 118:121-127.
• [31]Camp PG, Coxson HO, Levy RD, Pillai SG, Anderson W, Vestbo J, Kennedy SM, Silverman EK, Lomas DA, Pare PD: Sex differences in emphysema and airway disease in smokers. Chest 2009, 136:1480-1488.
• [32]Sverzellati N, Calabro E, Randi G, La Vecchia C, Marchiano A, Kuhnigk JM, Zompatori M, Spagnolo P, Pastorino U: Sex differences in emphysema phenotype in smokers without airflow obstruction. Eur Respir J 2009, 33:1320-1328.
• [33]Martinez FJ, Curtis JL, Sciurba F, Mumford J, Giardino ND, Weinmann G, Kazerooni E, Murray S, Criner GJ, Sin DD, Hogg J, Ries AL, Han M, Fishman AP, Make B, Hoffman EA, Mohsenifar Z, Wise R: Sex differences in severe pulmonary emphysema. Am J Respir Crit Care Med 2007, 176:243-252.
• [34]Dransfield MT, Washko GR, Foreman MG, Estepar RS, Reilly J, Bailey WC: Gender differences in the severity of CT emphysema in COPD. Chest 2007, 132:464-470.
• [35]Gevenois PA, Scillia P, de Maertelaer V, Michils A, De Vuyst P, Yernault JC: The effects of age, sex, lung size, and hyperinflation on CT lung densitometry. AJR Am J Roentgenol Radium 1996, 167:1169-1173.
• [36]Bellemare F, Jeanneret A, Couture J: Sex differences in thoracic dimensions and configuration. Am J Respir Crit Care Med 2003, 168:305-312.
• [37]Han MK, Kazerooni EA, Lynch DA, Liu LX, Murray S, Curtis JL, Criner GJ, Kim V, Bowler RP, Hanania NA, Anzueto AR, Make BJ, Hokanson JE, Crapo JD, Silverman EK, Martinez FJ, Wasko GR: Chronic obstructive pulmonary disease exacerbations in the COPDGene study: associated radiologic phenotypes. Radiology 2011, 261:274-282.
• [38]Camiciottoli G, Bigazzi F, Paoletti M, Cestelli L, Lavorini F, Pistolesi M: Pulmonary function and sputum characteristics predict computed tomography phenotype and severity of COPD. Eur Respir J 2013, 42:626-635.
• [39]Hogg JC: Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 2004, 364:709-721.