A probabilistic model of biological ageing of the lungs for analysing the effects of smoking, asthma and COPD

Respiratory Research

Timothy David Spector²  Hannah Tipney¹  Ana Viñuela²  John Winn³  Silvia Chiappa³ 

[1] Current address: GlaxoSmithKline Research & Development Ltd, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK;Department of Twin Research & Genetic Epidemiology, King’s College London, Westminster Bridge Road, London SE1 7EH, UK;Microsoft Research Cambridge, 21 Station Road, Cambridge CB1 2FB, UK

关键词: FVC;    FEV₁;    COPD;    Asthma;    Smoking;    Posterior distributions;    Generative model;    Probabilistic model;    Biological ageing;    Lung function;   

Others  :  794529
DOI  :  10.1186/1465-9921-14-60

 received in 2012-12-20, accepted in 2013-05-03,  发布年份 2013

【 摘 要 】

Background

Although a large body of literature is available that describes the effects of smoking, asthma and COPD on lung function, most studies are restricted to a small age range and to one factor. As a consequence, available results are incomplete and often difficult to compare, also due to the ways the effects are expressed. Furthermore, current approaches consider one type of measurement only or several types separately.

Methods

We propose a probabilistic model that expresses the effects as number of years added to chronological age or, in other words, that estimates the biological age of the lungs. Using biological age as a measure of the effects has the advantage of facilitating the understanding of their severity and comparison of results. In our model, chronological age and other factors affecting the health status of the lungs generate biological age, which in turn generates lung function measurements. This structure enables the use of multiple types of measurement to obtain a more precise estimate of the effects and parameter sharing for characterization over large age ranges and of co-occurrence of factors with little data. We treat the parameters that model smoking habits and lung diseases as random variables to obtain uncertainty in the estimated effects.

Results

We use the model to investigate the effects of smoking, asthma and COPD on the TwinsUK Registry. Our results suggest that the combination of smoking with lung disease(s) has higher effect than smoking or lung disease(s) alone, and that, in smokers, co-occurrence of asthma and COPD is more detrimental than asthma or COPD alone.

Conclusions

The proposed model or other models based on a similar approach could be of help in improving the understanding of factors affecting lung function by enabling characterizations over large age ranges and of co-occurrence of factors with little data and the use of multiple types of measurement. The software implementing the model can be downloaded at the first author’s webpage.

【 授权许可】

   
2013 Chiappa et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 4.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Sherrill DL, Lebowitz MD, Knudson RJ, Burrows B: Smoking and symptom effects on the curves of lung function growth and decline. Am Rev Respir Dis 1991, 144:17-22.
• [2]Kerstjens HA: Decline of FEV1 by, age and smoking status: facts, figures, and fallacies. Thorax 1997, 52(9):820-827.
• [3]Willemse BWM, Postma DS, Timens W, ten Hacken NHT: The impact of smoking cessation on respiratory symptoms, lung function, airway hyperresponsiveness and inflammation. Eur Respir J 2004, 23(3):464-476.
• [4]James AL, Palmer LJ, Kicic E, Maxwell PS, Lagan SE, Ryan GF, Musk AW: Decline in lung function in the Busselton Health Study: the effects of asthma and cigarette smoking. Am J Respir Crit Care Med 2005, 171(2):109-114.
• [5]Sears MR: Lung function decline in asthma. Eur Respir J 2007, 30(3):411-413.
• [6]Lee PN, Fry JS: Systematic review of the evidence relating FEV1 decline to giving up smoking. BMC Med 2010, 8:84-112. BioMed Central Full Text
• [7]Drummond MB, Hansel NN, Connett JE, Scanlon PD, Tashkin DP, Wise RA: Spirometric predictors of lung function decline and mortality in early chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012, 185(12):1301-1306.
• [8]MacDonald SWS, Dixon RA, Cohen AL, Hazlitt JE: Biological age and 12-year cognitive change in older adults: findings from the Victoria Longitudinal Study. Gerontology 2004, 50(2):64-81.
• [9]Klemera P, Doubal S: A new approach to the concept and computation of biological age. Mech Ageing Dev 2006, 127(3):240-248.
• [10]Knowles DA, Part sL, Glass D, Winn JM: Inferring a measure of physiological age from multiple ageing related phenotypes. 2011. [NIPS Workshop From Statistical Genetics to Predictive Models in Personalized Medicine]
• [11]Morris JF, Temple W: Lung age estimation for motivating smoking cessation. Prev Med 1985, 14:655-662.
• [12]Parkes G, Greenhalgh T, Griffin M, Dent R: Effect of smoking on FEV1 decline in a cross-sectional and longitudinal study of a large cohort of Japanese males. BMJ 2008, 336:598-600.
• [13]Bize R, Burnand B, Mueller Y, Rège-Walther M, Camain JY, Cornuz J: Biomedical risk assessment as an aid for smoking cessation. Cochrane Database Syst Rev 2012., 12CD004705
• [14]Moayyeri A, Hammond CJ, Valdes AM, Spector TD: Cohort profile: TwinsUK and healthy ageing twin study. Int J Epidemiol 2013, 42:76-85.
• [15]Falaschetti E, Laiho J, Primatesta P, Purdon S: Prediction equations for normal and low lung function from the Health Survey for England. Eur Respir J 2004, 23(3):456-463.
• [16]Stanojevic S, Wade A, Stocks J, Hankinson J, Coates AL, Pan H, Rosenthal M, Corey M, Lebecque P, Cole TJ: Reference ranges for spirometry across all ages: a new approach. Am J Respir Crit Care Med 2008, 177(3):253-260.
• [17]Zhai G, Valdes AM, Cherkas L, Clement G, Strachan D, Spector TD: The interaction of genes and smoking on forced expiratory volume: a classic twin study. Chest 2007, 132(6):1772-1777.
• [18]Wypij D: Spline and smoothing approaches to fitting flexible models for the analysis of pulmonary function data. Am J Respir Crit Care Med 1996, 154:S223-S228.
• [19]Brändli O, Schindler C, Künzli N, Keller R, Perruchoud AP: Lung function in healthy never smoking adults: reference values and lower limits of normal of a Swiss population. Thorax 1996, 51(3):277-283.
• [20]Ulrik CS, Lange P: Decline of lung function in adults with bronchial asthma. Am J Respir Crit Care Med 1994, 150(3):629-634.
• [21]Xu X, Weiss ST, Rijcken B, Schouten JP: Smoking, changes in smoking habits, and rate of decline in FEV1: new insight into gender differences. Eur Respir J 1994, 7(6):1056-1061.
• [22]Xu X, Li B, Wang L: Gender difference in smoking effects on adult pulmonary function. Eur Respir J 1994, 7(3):477-483.
• [23]Peat JK, Woolcock AJ, Cullen K: Decline of lung function and development of chronic airflow limitation: a longitudinal study of non-smokers and smokers in Busselton, Western Australia. Thorax 1990, 45:32-37.
• [24]Anthonisen NR, Connett JE, Murray RP: Smoking and lung function of lung health study participants after 11 years. Am J Respir Crit Care Med 2002, 166(5):675-679.
• [25]Chen Y, Horne SL, Dosman JA: Increased susceptibility to lung dysfunction in female smokers. Am Rev Respir Dis 1991, 143(6):1224-1230.
• [26]Langhammer A, Johnsen R, Gulsvik A, Holmen TL, Bjermerz L: Sex differences in lung vulnerability to tobacco smoking. Eur Respir J 2003, 21(6):1017-1023.
• [27]Kohansal R, Martinez-Camblor P, Buist AS, Mannino DM, Soriano JB, Agustí A: The natural history of chronic airflow obstruction revisited: an analysis of the Framingham offspring cohort. Am J Respir Crit Care Med 2009, 180:3-10.
• [28]Cole TJ, Green PJ: Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 1992, 11(10):1305-1319.
• [29]Hughes JA, Hutchison DC, Bellamy D, Dowd DE, Ryan KC, Hugh-Jones P: Annual decline of lung function in pulmonary emphysema: influence of radiological distribution. Thorax 1982, 37:32-37.
• [30]Lange P, Parner J, Vestbo J, Schnohr P, Jensen G: A 15-year follow-up study of ventilatory function in adults with asthma. New England J Med 1998, 339(17):1194-1200.
• [31]Gibson PJ, Simpson JL: The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax 2009, 64:728-735.
• [32]Kauppi P, Kupiainen H, Lindqvist A, Tammilehto L, Kilpeläinen M, Kinnula VL, Haahtela T, Laitinen T: Overlap syndrome of asthma and COPD predicts low quality of life. J Asthma 2011, 48(3):279-285.
• [33]Hardin M, Silverman EK, Barr RG, Hansel NN, Schroeder JD, Make BJ, Crapo JD, Hersh CP: The clinical features of the overlap between COPD and asthma. Respir Res 2011, 12:127-134. BioMed Central Full Text
• [34]McLachlan GJ, Krishnan T: The EM Algorithm and Extensions. Hoboken: John Wiley & Sons; 2008.