**13. Recent advances**

COPD is an area of intensive research, reporting important advances in the understanding of and care for the disease. Evidence from recent epidemiological studies have questioned the diagnostic value of the GOLD criteria of fixed FEV1/FVC threshold of 0.7 defining airflow limitation. These studies have demonstrated high false-negative rate in young subjects at risk and the false-positive rate in older patients(Cerveri et al.,2008;Hansen et al.,2007 as cited in Bourdin A,2009). The lower limit of normal(LLN) as recommended by American Thoracic Society(ATS) and European Respiratory Society(ERS) seems to be much more reliable for defining obstruction, particularly for screening purposes(Swanney et al.,2008 as cited in ATS,2010). The criteria of reversibility of airflow obstruction to differentiate COPD from asthma has come under question based on wide range of reversibility demonstrated in UPLIFT trial (Tashkin et al.,2008).

Some consider COPD as a component of a broader syndrome that was called ''chronic systemic inflammatory syndrome''. Patients are diagnosed with this syndrome if they have three or more components of the following: age >40 yrs, smoking history >10 pack-yrs, symptoms and abnormal lung function compatible with COPD, chronic heart failure, metabolic syndrome and increased CRP(Fabbri & Rabe,2007 as cited in Bourdin A,2009).

New evidence has enhanced the understanding of oxidative stress, injury and protective antioxidants such as the glutathione system and the haemoxygenase(HO)-1 pathway. Reduced HO-1 expression has been described in macrophages from lung tissue and bronchoalveolar lavage (BAL) of smokers with COPD(Maestrelli et al.,2003;Slebos et al.,2004 as cited in Bourdin A,2009).Moreover, the subtle molecular regulation of HO-1 and its key protein regulators, such as Nrf2, Bach1 and Keap1, is modified in COPD. Nrf2 protein level is significantly decreased in whole lung tissue and alveolar macrophages and conversely, Bach1 and Keap1 levels were increased in patients with emphysema (Goven et al.,2008 as cited in Bourdin A,2009).

A specific antigen reaction is a hypothesis put forward in order to better understand COPD progression; T-cells(both CD4 & CD8) may play a role in this possible B-cell mediated response. Leptin has been described as a potential regulator of lymphocyte lifespan within the airways of COPD patients(Bruno et al.,2005). The production of RANTES (regulated upon activation, normal T-cell expressed and secreted) is increased, as shown in the sputum of patients with COPD. Regulatory T-cells (Tregs) are special T-lymphocytes that are important for preventing autoimmune reactions by inhibiting T-cell responses (Baraldo &

(Redelmeir et al.,1997 as cited in Shapiro SD,2010). The shuttle walk test offers the advantages of being perfectly standardized and highly related to peak oxygen consumption. Health status is mostly impaired by exacerbations on the one hand and dyspnoea on the other, with its negative effect on daily activity. Some extrapulmonary parameters are also correlated with measures of daily activity, independent of GOLD stage and BODE score; they include left cardiac dysfunction (as assessed by levels of B-type natriuretic peptide and echocardiography) and systemic inflammation (C-reactive protein levels) (Watz et al.,2008 as cited in Shapiro SD,2010). Frequent exacerbations have a negative long-term impact on the BODE index, a well known prognostic factor in COPD, and are not purely respiratory

COPD is an area of intensive research, reporting important advances in the understanding of and care for the disease. Evidence from recent epidemiological studies have questioned the diagnostic value of the GOLD criteria of fixed FEV1/FVC threshold of 0.7 defining airflow limitation. These studies have demonstrated high false-negative rate in young subjects at risk and the false-positive rate in older patients(Cerveri et al.,2008;Hansen et al.,2007 as cited in Bourdin A,2009). The lower limit of normal(LLN) as recommended by American Thoracic Society(ATS) and European Respiratory Society(ERS) seems to be much more reliable for defining obstruction, particularly for screening purposes(Swanney et al.,2008 as cited in ATS,2010). The criteria of reversibility of airflow obstruction to differentiate COPD from asthma has come under question based on wide range of

Some consider COPD as a component of a broader syndrome that was called ''chronic systemic inflammatory syndrome''. Patients are diagnosed with this syndrome if they have three or more components of the following: age >40 yrs, smoking history >10 pack-yrs, symptoms and abnormal lung function compatible with COPD, chronic heart failure, metabolic syndrome and increased CRP(Fabbri & Rabe,2007 as cited in Bourdin A,2009).

New evidence has enhanced the understanding of oxidative stress, injury and protective antioxidants such as the glutathione system and the haemoxygenase(HO)-1 pathway. Reduced HO-1 expression has been described in macrophages from lung tissue and bronchoalveolar lavage (BAL) of smokers with COPD(Maestrelli et al.,2003;Slebos et al.,2004 as cited in Bourdin A,2009).Moreover, the subtle molecular regulation of HO-1 and its key protein regulators, such as Nrf2, Bach1 and Keap1, is modified in COPD. Nrf2 protein level is significantly decreased in whole lung tissue and alveolar macrophages and conversely, Bach1 and Keap1 levels were increased in patients with emphysema (Goven et al.,2008 as

A specific antigen reaction is a hypothesis put forward in order to better understand COPD progression; T-cells(both CD4 & CD8) may play a role in this possible B-cell mediated response. Leptin has been described as a potential regulator of lymphocyte lifespan within the airways of COPD patients(Bruno et al.,2005). The production of RANTES (regulated upon activation, normal T-cell expressed and secreted) is increased, as shown in the sputum of patients with COPD. Regulatory T-cells (Tregs) are special T-lymphocytes that are important for preventing autoimmune reactions by inhibiting T-cell responses (Baraldo &

episodes but associated with systemic inflammation.

reversibility demonstrated in UPLIFT trial (Tashkin et al.,2008).

**13. Recent advances** 

cited in Bourdin A,2009).

Saetta,2008 as cited in Bourdin A,2009). The best described population of Treg is CD4+, and expresses CD25 and a transcription factor FOXP3.

Scores used in clinical practice to assess health status have been modified to be useful in primary care setting. The simplified version of the original BODE index, BOD score and a new index called ADO(age, dyspnoea and airflow obstruction) have been studied and found to have similar accuracy for risk prediction(Puhan et al.,2009 as cited in Bourdin A,2009).

Thoracic gas compression during forced expiration is a major event in COPD and a new index of gas compression defined as (NFEV1-FEV1)/NFEV1 (in percent) was demonstrated to be higher at baseline in COPD (32%) than in controls (10%) and it decreased after albuterol only in COPD patients. Shuttle walk test for exercise testing, negative expiratory pressure(NEP) method and forced oscillation technique(FOT) to measure expiratory flow limitation(EFL), single-breath nitrogen washout test(SBN2) for small airway involvement, inspiratory muscle endurance(IME) for monitoring respiratory muscle training, diaphragmatic electromyogram(EMG) for neural respiratory drive, etc include some of the modalities to assess clinical function, response to treatment and some for purely research evaluations.

Newer imaging techniques have recently allowed for the possibility of evaluating pulmonary function as well as anatomy. Although helical CT and HRCT have become the cornerstone of pulmonary imaging, newer modalities such as PET and MRI may soon become critical components in the arsenal of tests used to evaluate pulmonary disease. Newer axial CT is as accurate as fiberoptic bronchoscopy (FOB) and virtual bronchoscopy (VB), or CT bronchography, has received considerable attention and excellent internal images of the tracheobronchial tree can be generated to the level of the 4th-5th generation bronchi.

Increasing evidence in support of therapy with phosphodiesterase-4 inhibitors, antioxidants and augmentation therapy with A1PI in deficient individuals, seem promising. Nonrespiratory treatments of co-morbidities with medications such as proton pump inhibitors, angiotensin-converting enzyme inhibitors, and statins show promise in the management of COPD. Bronchoscopic lung volume reduction (bLVR) is being developed to collapse areas of emphysematous lung in hopes of having the same effect on respiratory function as LVRS, but without the morbidity and mortality of surgery. Safety and effectiveness of minimally invasive approaches like video-assisted thoracoscopy for the treatment of giant bullae is under evaluation.
