• Hafiz Muhammad Waseem University of Health Sciences, Lahore
  • Rida Ajmal Khan Azra Naheed Medical College, Lahore
  • Khalid Parvez Lone University of Health Sciences, Lahore


Background: Chronic Obstructive Pulmonary Disease (COPD) is the leading cause of morbidity and mortality across the globe. Currently, there is a dearth of biomarkers which can accurately diagnose and evaluate the prognosis of the disease. Systemic Surfactant Protein- A (SP-A) levels are generally higher in smokers compared to non-smokers as well as elevated in COPD patients as compared to controls. The objective of the study was to estimate and compare plasma surfactant protein-A levels in male and female COPD patients and healthy subjects and to evaluate the role of SP-A as a possible bio-marker for COPD patients. Methods: A Comparative study, conducted at the department of Physiology & Cell Biology, University of Health Sciences, Lahore between August 2013 and April 2015. A total of 84 subjects of both sexes between 30-80 years of age were included in this study. Subjects were taken from local community and were divided into four groups (A- D). COPD was diagnosed on the basis of relevant history and spirometry showing post bronchodilator FEV1/FVC <0.70. Results: Plasma SP-A levels were not different between controls and COPD patients and between male and female COPD patients. However, SP-A levels were directly correlated with cotinine levels (r= 0.503, p=0.001). Female patients were usually more symptomatic than males and developed COPD at an earlier age compared with male patients. Conclusion: Plasma SP-A levels were not significantly different between groups. Plasma cotinine levels (an indication of the tobacco use) were positively correlated with plasma SP-A levels in study subjects. Female patients developed COPD at an early age compared to male counterparts with similar tobacco exposure.Keywords: Chronic Obstructive Lung Disease, Surfactant Protein A, Cotinine, Spirometry, Smoking

Author Biographies

Hafiz Muhammad Waseem, University of Health Sciences, Lahore

PhD Scholar, Department of Physiology & Cell Biology, University of Health Sciences, Lahore.

Rida Ajmal Khan, Azra Naheed Medical College, Lahore

Assistant Professor, Department of Physiology, Azra Naheed Medical College, Lahore.

Khalid Parvez Lone, University of Health Sciences, Lahore

Professor & Head of Department, Department of Physiology & Cell Biology, University of Health Sciences, Lahore


WHO. Chronic respiratory diseases; Burden of COPD. [Internet]. World Health Organization; 2017. [cited 2017 Oct 4]. Available from:

van Geffen WH, Kerstjens HAM, Slebos DJ. Emerging bronchoscopic treatments for chronic obstructive pulmonary disease. Pharmacol Ther 2017;179:96–101.

Barnes PJ, Burney PGJ, Silverman EK, Celli BR, Vestbo J, Wedzicha JA, et al. Chronic obstructive pulmonary disease. Nature Reviews. Dis Primer 2015;1:15076.

Paulin LM, Diette GB, Blanc PD, Putcha N, Eisner MD, Kanner RE, et al. Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015;191(5):557–65.

El Hasnaoui A, Rashid N, Lahlou A, Salhi H, Doble A, Nejjari C. Chronic obstructive pulmonary disease in the adult population within the Middle East and North Africa region: rationale and design of the BREATHE study. Respir Med 2012;106(Suppl 2):S3–15.

Chen YW, Leung JM, Sin DD. A Systematic Review of Diagnostic Biomarkers of COPD Exacerbation. PLoS One 2016;11(7):e0158843.

Mazur W, Toljamo T, Ohlmeier S, Vuopala K, Nieminen P, Kobayashi H, et al. Elevation of surfactant protein A in plasma and sputum in cigarette smokers. Eur Respir J 2011;38(2):277–84.

Ilumets H, Mazur W, Toljamo T, Louhelainen N, Nieminen P, Kobayashi H, et al. Ageing and smoking contribute to plasma surfactant proteins and protease imbalance with correlations to airway obstruction. BMC Pulm Med 2011;11:19.

Delobel J, Rubin O, Prudent M, Crettaz D, Tissot JD, Lion N. Biomarker analysis of stored blood products: emphasis on pre-analytical issues. Int. J. Mol. Sci., 2010; 11(11): 4601-4617.

Dima E, Rovina N, Gerassimou C, Roussos C, Gratziou C. Pulmonary function tests, sputum induction, and bronchial provocation tests: diagnostic tools in the challenge of distinguishing asthma and COPD phenotypes in clinical practice. Int J Chron Obstruct Pulmon Dis 2010;5:287–96.

Shakoori TA, Sin DD, Ghafoor F, Bashir S, Bokhari SN. Serum surfactant protein D during acute exacerbations of chronic obstructive pulmonary disease. Dis Markers 2009;27(6):287–94.

Baig IM, Saeed W, Khalil KF. Post-tuberculous chronic obstructive pulmonary disease. J Coll Physicians Surg Pak 2010;20(8):542–4.

Dales RE, Vandemheen KL, Clinch J, Aaron SD. Spirometry in the primary care setting: influence on clinical diagnosis and management of airflow obstruction. Chest 2005;128(4):2443–7.

Tan WC, Sin DD, Bourbeau J, Hernandez P, Chapman KR, Cowie R, et al. Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study. Thorax 2015;70(9):822–29.

Gnatiuc L, Caramori G. COPD in nonsmokers: the biomass hypothesis--to be or not to be? Eur Respir J 2014;44(1):8–10.

Gunen H, Hacievliyagil SS, Yetkin O, Gulbas G, Mutlu LC, Pehlivan E. Prevalence of COPD: first epidemiological study of a large region in Turkey. Eur J Intern Med 2008;19(7):499–504.

Antuni JD, Barnes PJ. Evaluation of Individuals at Risk for COPD: Beyond the Scope of the Global Initiative for Chronic Obstructive Lung Disease. Chronic Obstr Pulm Dis 2016;3(3):653–67.

Aryal S, Diaz-Guzman E, Mannino DM. Influence of sex on chronic obstructive pulmonary disease risk and treatment outcomes. Int J Chron Obstruct Pulmon Dis 2014;9:1145–54.

Dienye P, Akani A, Okokon I. Respiratory effects of biomass fuel combustion on rural fish smokers in a Nigerian fishing settlement: A case control study. Afr Health Sci 2016;16(2):516–23.

Po JY, FitzGerald JM, Carlsten C. Respiratory disease associated with solid biomass fuel exposure in rural women and children: systematic review and meta-analysis. Thorax 2011;66(3):232–9.

Akhtar T, Ullah Z, Khan MH, Nazli R. Chronic bronchitis in women using solid biomass fuel in rural Peshawar, Pakistan. Chest 2007;132(5):1472–5.

de Oliveira JC, de Carvalho Aguiar I, de Oliveira Beloto AC, Santos IR, Filho FS, Sampaio LM, et al. Clinical significance in COPD patients followed in a real practice. Multidiscip Respir Med 2013;8(1):43.

Kessler R, Partridge MR, Miravitlles M, Cazzola M, Vogelmeier C, Leynaud D, et al. Symptom variability in patients with severe COPD: a pan-European cross-sectional study. Eur Respir J 2011;37(2):264–72.

Lim S, Lam DC, Muttalif AR, Yunus F, Wongtim S, Lan le TT, et al. Impact of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region: the EPIC Asia population-based survey. Asia Pac Fam Med 2015;14(1):4.

Halldin CN, Doney BC, Hnizdo E. Changes in prevalence of chronic obstructive pulmonary disease and asthma in the US population and associated risk factors. Chron Respir Dis 2015;12(1):47–60.

Robin M, Dong P, Hermans C, Bernard A, Bersten AD, Doyle IR. Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects. Eur Respir J 2002;20(5):1152–61.

Mutti A, Corradi M, Goldoni M, Vettori MV, Bernard A, Apostoli P. Exhaled metallic elements and serum pneumoproteins in asymptomatic smokers and patients with COPD or asthma. Chest 2006;129(5):1288–97.

Ohlmeier S, Vuolanto M, Toljamo T, Vuopala K, Salmenkivi K, Myllarniemi M, et al. Proteomics of human lung tissue identifies surfactant protein A as a marker of chronic obstructive pulmonary disease. J Proteome Res 2008;7(12):5125–32.

Ishikawa N, Hattori N, Tanaka S, Horimasu Y, Haruta Y, Yokoyama A, et al. Levels of surfactant proteins A and D and KL-6 are elevated in the induced sputum of chronic obstructive pulmonary disease patients: a sequential sputum analysis. Respiration 2011;82(1):10–8.

Liang S, Li N, Heizhati M, Yao X, Abdireim A, Wang Y, et al. What do changes in concentrations of serum surfactant proteins A and D in OSA mean? Sleep Breath 2015;19(3):955–62.

Greene KE, King TE Jr, Kuroki Y, Bucher-Bartelson B, Hunninghake GW, Newman LS, et al. Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis. Eur Respir J 2002;19(3):439–46.

Sin DD, Miravitlles M, Mannino DM, Soriano JB, Price D, Celli BR, et al. What is asthma-COPD overlap syndrome? Towards a consensus definition from a round table discussion. Eur Respir J 2016;48(3):664–73.

Sørheim IC, Johannessen A, Gulsvik A, Bakke PS, Silverman EK, DeMeo DL. Gender differences in COPD: are women more susceptible to smoking effects than men? Thorax 2010;65(6):480–5.

Behera D, Balamugesh T, Venkateswarlu D, Gupta A, Majumdar S. Serum surfactant protein-A levels in chronic bronchitis and its relation to smoking. Indian J Chest Dis Allied Sci 2005;47(1):13–7.

Benowitz NL, Hukkanen J, Jacob P 3rd. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol 2009;(192):29–60.

Alshaarawy O, Xiao J, Andrew ME, Burchfiel C, Shankar A. Serum cotinine levels and prehypertension in never smokers. Int J Hypertens 2013;2013:284524.