Airflow limitation, lung volumes and systemic inflammation in a general population

Although several levels of evidence have suggested an association between systemic inflammation and spirometric lung volumes, data addressing the potential interrelationship between airflow limitation and inflammatory markers are sparse and remain controversial. Potential associations between high-sensitivity C-reactive protein (hsCRP), fibrinogen and lung function were investigated in 1,466 individuals aged 25–85 yrs, representing a general population. Within this cross-sectional population, data on body plethysmography, spirometry, helium dilution and diffusing capacity of the lung for carbon monoxide (DL,CO) were analysed. After adjustment for potential confounding factors, such as smoking, obesity and cardiorespiratory fitness, there was an inverse association of hsCRP with forced expiratory and static lung volumes. In neither apparently healthy nor the entire population was inflammation associated with airflow limitation in central airways. In smokers only, higher hsCRP and fibrinogen were associated with an impaired DL,CO. This study shows that higher levels of hsCRP are associated with decreased lung volumes in a general population over a wide age range. A consistent interrelationship of central airflow limitation and inflammation was not verifiable. Smoking is related to an impaired DL,CO in association with an increase in systemic inflammation.

[1]  J E Cotes,et al.  Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. , 1993, The European respiratory journal. Supplement.

[2]  H. Völzke,et al.  [Reference values for lung function testing in adults--results from the study of health in Pomerania" (SHIP)]. , 2009, Deutsche medizinische Wochenschrift.

[3]  M. Kenward,et al.  Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls , 2009, BMJ : British Medical Journal.

[4]  J. Roca,et al.  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. , 1993, The European respiratory journal. Supplement.

[5]  S. Cummings,et al.  The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women. , 2003, The American journal of medicine.

[6]  C. Lewis,et al.  Plasma fibrinogen and lung function: the CARDIA Study. , 2006, International journal of epidemiology.

[7]  K. Schultz,et al.  [Guidelines for the diagnosis and therapy of COPD issued by Deutsche Atemwegsliga and Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin]. , 2007, Pneumologie.

[8]  T H Beaty,et al.  Impaired pulmonary function as a risk factor for mortality. , 1982, American journal of epidemiology.

[9]  R. Poulton,et al.  Systemic inflammation and lung function in young adults , 2007, Thorax.

[10]  W. Rathmann,et al.  Cohort profile: the study of health in Pomerania. , 2011, International journal of epidemiology.

[11]  J. Barberà,et al.  Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity. , 2009, Journal of applied physiology.

[12]  S. Rubin,et al.  Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects , 2005, Thorax.

[13]  P. Elliott,et al.  Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels , 2011, Circulation.

[14]  Dan Xu,et al.  Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters , 2010, Respiratory research.

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

[16]  R M Gardner,et al.  Performance evaluation of contemporary spirometers. , 1990, Chest.

[17]  M. Cosio,et al.  Detection of expiratory flow limitation during exercise in COPD patients. , 1997, Journal of applied physiology.

[18]  Buist As Standardization of spirometry. , 1987 .

[19]  K. Nakashima,et al.  [The Rotterdam study]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.

[20]  Standardization of spirometry--1987 update. Official statement of American Thoracic Society. , 1987, Respiratory care.

[21]  H. Völzke,et al.  Lung function reference values in different German populations. , 2011, Respiratory medicine.

[22]  A. Clauss,et al.  Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens , 1957 .

[23]  Konrad Schultz,et al.  Leitlinie der Deutschen Atemwegsliga und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD) , 2007 .

[24]  Henry Völzke,et al.  Association of posttraumatic stress disorder with low-grade elevation of C-reactive protein: evidence from the general population. , 2010, Journal of psychiatric research.

[25]  H. Boshuizen,et al.  Multiple imputation of missing blood pressure covariates in survival analysis. , 1999, Statistics in medicine.

[26]  Organización Mundial de la Salud Guidelines for ATC classification and DDD assignment , 1996 .

[27]  Inês Barroso,et al.  Genome-wide association study identifies five loci associated with lung function , 2010, Nature Genetics.

[28]  Albert Hofman,et al.  Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. , 2004, European heart journal.

[29]  J. Roca,et al.  Standardization of the measurement of transfer factor (diffusing capacity) , 1993, European Respiratory Journal.

[30]  J E Cotes,et al.  Lung volumes and forced ventilatory flows , 1993, European Respiratory Journal.

[31]  G. Viegi,et al.  Standardisation of the measurement of lung volumes , 2005, European Respiratory Journal.

[32]  H. Magnussen,et al.  The metabolic syndrome in patients with chronic bronchitis and COPD: frequency and associated consequences for systemic inflammation and physical inactivity. , 2009, Chest.

[33]  A. Clauss [Rapid physiological coagulation method in determination of fibrinogen]. , 1957, Acta haematologica.

[34]  A. Eggen,et al.  Bronchial airflow limitation, smoking, body mass index, and statin use are strongly associated with the C-reactive protein level in the elderly. The Tromsø Study 2001. , 2007, Respiratory medicine.

[35]  P. Schnohr,et al.  Spirometric findings and mortality in never-smokers. , 1990, Journal of clinical epidemiology.

[36]  K. Godfrey,et al.  Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease. , 1991, BMJ.

[37]  M. Noppen,et al.  Conductive and acinar lung-zone contributions to ventilation inhomogeneity in COPD. , 1998, American journal of respiratory and critical care medicine.

[38]  P. O'Byrne,et al.  Is nedocromil sodium effective treatment for asthma? , 1993, The European respiratory journal.

[39]  A. Buist,et al.  Chronic airflow obstruction and markers of systemic inflammation: results from the BOLD study in Iceland. , 2009, Respiratory medicine.

[40]  Referenzwerte für die Spirometrie bei Erwachsenen Ergebnisse der „Study of Health in Pomerania (SHIP) , 2009 .

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

[42]  F. Rasmussen,et al.  High-sensitive C-reactive protein is associated with reduced lung function in young adults , 2008, European Respiratory Journal.

[43]  G. Watt,et al.  Inverse Association Between Birth Weight and C-Reactive Protein Concentrations in the MIDSPAN Family Study , 2004, Arteriosclerosis, Thrombosis and Vascular Biology.

[44]  W. Markiewicz,et al.  Factor analysis of risk variables associated with low-grade inflammation. , 2008, Atherosclerosis.

[45]  Patrick Royston,et al.  Multivariable Model-Building: A Pragmatic Approach to Regression Analysis based on Fractional Polynomials for Modelling Continuous Variables , 2008 .

[46]  J. Hankinson,et al.  Standardisation of the single-breath determination of carbon monoxide uptake in the lung , 2005, European Respiratory Journal.

[47]  J. E. Hansen,et al.  Spirometric criteria for airway obstruction: Use percentage of FEV1/FVC ratio below the fifth percentile, not < 70%. , 2007, Chest.