**4.4.4 Pulmonary interstitial emphysema**

Collection of gases outside of the normal air passages and inside the connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura may result from alveolar or bronchiolar rupture commonly in premature infants on mechanical ventilation. It is a radiographic and pathologic diagnosis frequently in conjunction with respiratory distress syndrome, meconium aspiration syndrome, amniotic fluid aspiration and infection.

#### **4.4.5 Acute generalized overinflation of the lung**

Usually reported in infants and children secondary to a number of clinical conditions affecting bronchioles, including asthma, cystic fibrosis, acute bronchiolitis, interstitial pneumonitis, atypical forms of acute laryngotracheobronchitis, aspiration of zinc stearate powder, chronic passive congestion secondary to a congenital cardiac lesion, and miliary tuberculosis.

Current Overview of COPD with Special Reference to Emphysema 127

particularly elastases such as MMP-9 and MMP-12, resulting in lung tissue injury. Degraded elastin fragments are chemotactic for macrophages, thus ensuing a self-propagating

T cells lympocytes, especially CD8+ cells are increased in airway walls and alveoli of patients with COPD(Saetta et al.,1998 as cited in Shapiro SD,2010). Airway epithelial cells in smokers with COPD have increased expression of CXCL10 (IP-10), the ligand for CXCR3 found on CD8+Tcells and thus may be the activation pathway for macrophages to produce MMP-12(Grumelli et al.,2004;Saetta et al.,2002 as cited in Shapiro SD,2010). Cytotoxic T cells may target epithelial cells and induce cell death, particularly those with (latent) viral

Elastin fragments can serve as autoantigens and immunoglobulin G (IgG) autoantibodies with avidity for pulmonary epithelium have been found in patients with COPD(Feghali-Bostwick et al.,2008;Lee et al.,2007 as cited in Shapiro SD,2010). Increased numbers of B cells and lymphoid follicles in the lung have raised interest in a possible autoimmune pathogenesis of COPD(Curtis et al.,2007;Taraseviciene-Stewart & Voelkel,2008 as cited in Shapiro SD,2010). Interplay of all these inflammatory pathways results in the tissue damage

Elastin and collagen is critical to the structural integrity of the lung. Experimental studies in animal lung models with instilled proteinases have replicated emphysematous changes(Gross et al.,1964 as cited in Shapiro SD,2010) resulting in an initial rapid increase in air space size due to direct elastolysis with diminution of lung elastin content at 24 hours followed by rapid restoration of total lung elastin to normal levels(Janoff et al.,1977;Snider et al.,1984 as cited in Shapiro SD,2010). The anatomic arrangement of the restored elastic fibers is grossly disordered (Kuhn & Senior,1978 as cited in Shapiro SD,2010). The tissue displays inflammation with neutrophils and macrophages with subsequent release of endogenous inflammatory mediators including IL-1β and TNF-α with endogenous proteolytic progression of the disease. Based on these studies and the association between A1PI deficiency with emphysema(Laurell & Eriksson,1963 as cited in Shapiro SD,2010), the proteinase-antiproteinase hypothesis proposed that the balance between matrix-degrading proteinases and their endogenous inhibitors determines whether the lung is protected or

Some proteinases such as NE and MMP-9 are bound to the surface of the neutrophil, they are resistant to complete inhibition by A1PI and tissue inhibitors of metalloproteinases (TIMPs). "Microenvironmental" concentration of proteinases and their proximity to the target site of matrix proteins when released from the neutrophil and macrophages, may explain how the balance tilts towards the proteinase function even in presence of adequate overall anti-proteinase in circulation(Owen & Campbell,1999 as cited in Shapiro SD,2010).

The serine proteinase Neutrophil elastase(NE) is suspected to be the major causative agent of tissue injury in COPD after the findings that patients deficient in its endogenous

There are four classes of proteinases, serine, cysteine, aspartic, and MMPs:

cycle(Houghton et al.,2006;Senior et al.,1980 as cited in Shapiro SD,2010).

infection.

that keeps adding up over the years.

susceptible to proteolytic injury.

**5.2.1 Serine proteinases** 

**5.2 Proteinase-antiproteinase imbalance** 

### **4.4.6 Bullous emphysematous blebs or cysts (pneumatoceles)**

They result from overdistention and rupture of alveoli during birth, or as sequelae of pneumonia and other infections. They have been observed in tuberculosis lesions during specific antibacterial therapy.
