On the role of abnormal DLCO in ex-smokers without airflow limitation: symptoms, exercise capacity and hyperpolarised helium-3 MRI

Background The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood. Objective We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD. Methods We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St George's Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and hyperpolarised helium-3 (3He) MRI. The 6MWT distance (6MWD), SGRQ scores, 3He MRI apparent diffusion coefficients (ADC) and CT attenuation values below −950 HU (RA950) were evaluated. Results Of 38 ex-smokers without COPD, 19 subjects had abnormal DLCO with significantly worse ADC (p=0.01), 6MWD (p=0.008) and SGRQ (p=0.01) but not RA950 (p=0.53) compared with 19 ex-smokers with normal DLCO. Stage I COPD subjects showed significantly worse ADC (p=0.02), RA950 (p=0.0008) and 6MWD (p=0.005), but not SGRQ (p=0.59) compared with subjects with abnormal DLCO. There was a significant correlation for 3He ADC with SGRQ (r=0.34, p=0.02) and 6MWD (r=−0.51, p=0.0002). Conclusions In ex-smokers with normal spirometry and CT but abnormal DLCO, there were significantly worse symptoms, 6MWD and 3He ADC compared with ex-smokers with normal DLCO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DLCO and hyperpolarised 3He MRI in ex-smokers without COPD.

[1]  E. Silverman,et al.  Sex differences in emphysema and airway disease in smokers. , 2009, Chest.

[2]  G. Parraga,et al.  Hyperpolarized ³He magnetic resonance imaging: preliminary evaluation of phenotyping potential in chronic obstructive pulmonary disease. , 2011, European journal of radiology.

[3]  D. DeMeo,et al.  Gender differences in COPD: are women more susceptible to smoking effects than men? , 2010, Thorax.

[4]  F. Martinez,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[5]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[6]  D. Yablonskiy,et al.  MR imaging of diffusion of 3He gas in healthy and diseased lungs , 2000, Magnetic resonance in medicine.

[7]  R. West,et al.  Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive pulmonary disease in a nationally representative population sample , 2006, Thorax.

[8]  Neil Woodhouse,et al.  Emphysematous changes and normal variation in smokers and COPD patients using diffusion 3He MRI. , 2005, European journal of radiology.

[9]  E. Regan,et al.  Early-onset chronic obstructive pulmonary disease is associated with female sex, maternal factors, and African American race in the COPDGene Study. , 2011, American journal of respiratory and critical care medicine.

[10]  Aaron Fenster,et al.  Hyperpolarized 3He Ventilation Defects and Apparent Diffusion Coefficients in Chronic Obstructive Pulmonary Disease: Preliminary Results at 3.0 Tesla , 2007, Investigative radiology.

[11]  W. Thurlbeck,et al.  The National Institutes of Health Intermittent Positive Pressure Breathing trial--pathology studies. III. The diagnosis of emphysema. , 1987, The American review of respiratory disease.

[12]  G. Parraga,et al.  Evaluating bronchodilator effects in chronic obstructive pulmonary disease using diffusion-weighted hyperpolarized helium-3 magnetic resonance imaging. , 2012, Journal of applied physiology.

[13]  P. Jones,et al.  A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. , 1992, The American review of respiratory disease.

[14]  L W Hedlund,et al.  Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part I: Diffusion coefficient , 1999, Magnetic resonance in medicine.

[15]  E. Pozzi,et al.  “Nonobstructive” emphysema of the lung , 2007 .

[16]  P. Paré,et al.  Computed tomographic measurements of airway dimensions and emphysema in smokers. Correlation with lung function. , 2000, American journal of respiratory and critical care medicine.

[17]  N J Morrison,et al.  Limitations of computed tomography in the assessment of emphysema. , 1989, The American review of respiratory disease.

[18]  D. Cockcroft,et al.  Severe centrilobular emphysema in a patient without airflow obstruction. , 2002, Chest.

[19]  E. Regan,et al.  Clinical and radiographic predictors of GOLD-unclassified smokers in the COPDGene study. , 2011, American journal of respiratory and critical care medicine.

[20]  J. Mezey,et al.  Circulating endothelial microparticles as a measure of early lung destruction in cigarette smokers. , 2011, American journal of respiratory and critical care medicine.

[21]  P De Vuyst,et al.  Comparison of computed density and microscopic morphometry in pulmonary emphysema. , 1996, American journal of respiratory and critical care medicine.

[22]  A. Plummer The carbon monoxide diffusing capacity: clinical implications, coding, and documentation. , 2008, Chest.

[23]  Joanne Shannon,et al.  Physiologic basis of respiratory disease , 2005 .

[24]  Miranda Kirby,et al.  Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation. , 2012, Academic radiology.

[25]  Karl Swedberg,et al.  Six minute walk test. , 2005, European heart journal.

[26]  Sean B Fain,et al.  Early emphysematous changes in asymptomatic smokers: detection with 3He MR imaging. , 2006, Radiology.

[27]  Grace Parraga,et al.  Anatomical distribution of 3He apparent diffusion coefficients in severe chronic obstructive pulmonary disease , 2007, Journal of magnetic resonance imaging : JMRI.

[28]  N. Chin,et al.  A 39-year-old smoker with effort dyspnea, normal spirometry results, and low diffusing capacity. , 1998, Chest.

[29]  N. Müller,et al.  "Density mask". An objective method to quantitate emphysema using computed tomography. , 1988, Chest.

[30]  S. Springmeyer,et al.  Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience. , 1991, Chest.

[31]  J. Hankinson,et al.  Interpretative strategies for lung function tests , 2005, European Respiratory Journal.

[32]  R. Christie Emphysema of the Lungs—I* , 1944, British medical journal.

[33]  Comparison of single breath carbon monoxide diffusing capacity and pressure-volume curves in detecting emphysema. , 1990, The American review of respiratory disease.

[34]  J R MacFall,et al.  Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part II: T∗︁2 , 1999, Magnetic resonance in medicine.

[35]  Per Wollmer,et al.  Hyperpolarized 3He apparent diffusion coefficient MRI of the lung: Reproducibility and volume dependency in healthy volunteers and patients with emphysema , 2008, Journal of magnetic resonance imaging : JMRI.

[36]  Edwin J R van Beek,et al.  MRI of helium‐3 gas in healthy lungs: Posture related variations of alveolar size , 2004, Journal of magnetic resonance imaging : JMRI.

[37]  G Gamsu,et al.  High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity. , 1992, Radiology.

[38]  N. Adair,et al.  Exercise rehabilitation and chronic obstructive pulmonary disease stage. , 1999, American journal of respiratory and critical care medicine.

[39]  J. Hogg,et al.  Lung structure and function in cigarette smokers. , 1994, Thorax.

[40]  Dmitriy A Yablonskiy,et al.  Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema , 2006, Magnetic resonance in medicine.

[41]  T. W. van der Mark,et al.  Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension. , 2000, The European respiratory journal.

[42]  W. Thurlbeck Lung structure and function in cigarette smokers. , 1994, Thorax.

[43]  P. Leander,et al.  Validity of apparent diffusion coefficient hyperpolarized 3He-MRI using MSCT and pulmonary function tests as references. , 2009, European journal of radiology.

[44]  B. Celli,et al.  Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[45]  M. Matthay,et al.  Chest Medicine: Essentials of Pulmonary and Critical Care Medicine , 2011 .

[46]  J. Mugler,et al.  Healthy Nonsmokers Exposed Regularly To Secondhand Smoke Have Evidence Of Lung Injury Detected By Hyperpolarized Helium-3 Diffusion MRI , 2010, Asian Test Symposium.

[47]  W. Thurlbeck,et al.  The National Institutes of Health Intermittent Positive-Pressure Breathing Trial: Pathology Studies , 2015 .

[48]  A. Buist,et al.  Risk of over-diagnosis of COPD in asymptomatic elderly never-smokers , 2002, European Respiratory Journal.

[49]  M. Rubenfire,et al.  Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension. , 2001, The European respiratory journal.

[50]  P. Jones,et al.  The St George's Respiratory Questionnaire. , 1991, Respiratory medicine.

[51]  David B. Holiday,et al.  Altered exercise gas exchange and cardiac function in patients with mild chronic obstructive pulmonary disease. , 1993, Chest.