**3.1.5 Asthma**

120 Chronic Obstructive Pulmonary Disease – Current Concepts and Practice

United States are smokers (Mannino et al.,2002 as cited in Shapiro SD,2010). The estimated fraction of COPD mortality attributable to smoking was 54% for men 30–69 years of age and 52% for men 70 years of age or older (Ezzati & Lopez,2003 as cited in ATS,2010). There is a consistent exposure–response relationship which is demonstrated in evidence from cohort studies fulfilling the causal criterion of temporality (exposure preceding onset of disease). Although only 15% of smokers have clinically significant COPD, smoking leads to a predictable dose-dependent loss of lung function in pre-symptomatic phase which accelerates with age and has prognostic implications (Rennard & Vestbo,2006 as cited in Shapiro SD,2010). Smoking has supra-additive effect in worsening lung function and prognosis when combined with other risk factors like A1PI deficiency or occupational

Genetically determined deficiency of alpha1–protease inhibitor (A1PI) represents a proven genetic abnormality that predisposes to COPD(Ericksson,1964;Laurell & Eriksson,1963 as cited in Shapiro SD,2010). A1PI is inherited by codominant alleles on chromosomal segment 14q32.1. Early adult-onset emphysema associated with A1PI deficiency occurs most commonly with PiZZ (mutation in *SERPINA1* gene) phenotype. It is prevalent globally but most commonly found in whites of Northern European ancestry. Worldwide there are an estimated 116,000,000 carriers and 1,100,000 individuals with severe α1-AT deficiency.(Boas

Linkage analysis studies in early-onset COPD families have identified another serine proteinase inhibitor(serpin E2) on chromosome 2 as a potential defect site(DeMeo etal.,2006;Wilk et al.,2009 as cited in Shapiro SD,2010). Twin and familial aggregation studies suggest that genetic factors likely influence variation in pulmonary function in nonsmokers, but may not necessarily increase the risk of developing a clinical diagnosis of

Farming and occupations with dusty environments increase the risk of developing chronic bronchitis two to threefold and, in combination with smoking, the risk increases to almost sixfold above average population(Melbostad et al.,1997;Salvi & Barnes,2009 as cited in Shapiro SD,2010). Environmental particulate air pollution and indoor smoke from biomass fuels have also been linked to COPD (Tashkin et al.,1984). There is strong evidence of an association between outdoor pollution(particulate matter, O3,NO2) and decreased pulmonary function (Gauderman et al,2004,2007; Rojas-martinez et al.,2007 as cited in Shapiro SD,2010). Exposure to air pollutants, occupational exposure, second-hand smoke exposure, fumes from burning biomass fuel, etc can produce deleterious effects on the airway. Oxidative stress, pulmonary and systemic inflammation, reduction in airway ciliary activity, amplification of viral infections, and increases in bronchial reactivity could lead to

Epidemiological studies shows a male gender predominance related to the higher cigarette smoking habit or other inhaled toxins and occupational exposure among men within a

irreversible loss of pulmonary function over time and COPD(ATS,2010).

exposures(Silverman et al.,2009 as cited in Shapiro SD,2010).

**3.1.3 Occupational and environmental exposures** 

**3.1.2 Genetic predilection** 

& Winnie,2011)

COPD(ATS,2010).

**3.1.4 Gender** 

Accelerated loss of lung function has been noted among asthma patients(Lange et al.,1998; Peat et al.,1989 as cited in Shapiro SD,2010). Functional changes in both the small airways and the alveolar parenchyma have been reported. Many individuals have bronchial inflammation with features of both asthma and chronic bronchitis/emphysema( Gelb & Zamel,2000 as cited in Shapiro SD,2010).
