**7.1 History**

COPD is a gradually progressive chronic disease presenting with clinically obvious symptoms late in the course, usually in their fifth decade of life with productive cough or breathlessness or acute chest illness. A1PI-deficient patients present earlier than other COPD patients usually in 3rd-4th decades and by then they have significant liver disease, which usually starts in childhood.

Early COPD results in gradual progressive worsening of pulmonary function, which results in patients unknowingly avoiding exertional dyspnea (the most common early symptom of COPD) and fatigue by shifting their expectations and limiting their activity. Patients who have an extremely sedentary lifestyle but few complaints require further evaluation for possibility of underlying COPD as many patients reset their expectations with regard to health, termed "response shift"(Rennard et al,2002 as cited in Shapiro SD,2010). Generalised muscle weakness found in COPD patients can also contribute to this finding.

Most patients usually present in the fifth or sixth decade of life by when they have dyspnea with mild exertion and usually the forced expiratory volume in 1 second (FEV1) has fallen to 50% of predicted. Moderate to severe COPD patients report variability in symptoms over the course of the day or week-to-week; morning is typically the worst time of day. Dyspnea is related to both respiratory (hyperinflation and impaired gas exchange) and extrarespiratory (like muscle dysfunction, heart disease, anaemia and depression) features of COPD.

The chronic cough is characterized by the insidious onset of sputum production, which occurs in the morning initially, but may progress to occur throughout the day. The sputum is usually mucoid, but becomes purulent during exacerbations. Hemoptysis complicating chronic bronchitis usually occurs in association with acute exacerbation. Lung cancer and tuberculosis needs to be ruled out in this scenario(Thompson et al,1992 as cited in Shapiro SD,2010). Wheezing may also be found in some patients due to co-existence of asthma or COPD alone.

Acute exacerbations are characterized by increased cough, sputum, dyspnea, and fatigue, are increasingly frequent as the disease worsens. Each exacerbation may last for a few weeks and followed by prolonged recovery over months and may be difficult to distinguish from other causes of dypsnea, cough, and/or sputum including pneumonia, congestive heart failure, pulmonary embolism, or pneumothorax(Spencer & Jones,2003 as cited in Shapiro SD,2010).

A history of cigarette smoking or alternative inhalational exposure is usually found in majority of COPD patients. A1PI deficient patients may develop disease without smoking, however presence of smoking significantly worsens the course of disease. Some patients develop COPD without an obvious risk factor. Other historical features that may accompany COPD include certain comorbidities (eg, lung cancer, coronary artery disease, osteoporosis, depression, skeletal muscle weakness). Although most patients are usually obese, weight loss can also occur in COPD and is associated with a worse prognosis.
