Reliable epidemiological data regarding the burden of AE-COPD in the ER are lacking from India. Even less is known regarding the clinical presentation and outcome of AE-COPD in a predominantly bidi smoking population similar to the patients included in the present study. Observations from the present study indicate that patients with AE-COPD had one or more co-morbid conditions and metabolic abnormalities at presentation. High prevalence of past pulmonary TB was observed and active pulmonary TB was identified to be an important infective cause of AE-COPD.
Bidi smoking is more common in lower and middle income groups especially those residing in smaller towns, and rural areas of India as bidis are cheaper than cigarettes. Furthermore, bidi smoking is considered to cause about two to three times greater nicotine and tar inhalation than do conventional cigarettes, due to the poor combustibility of the bidi and greater puff frequency needed to keep the bidi alight . All these factors may exaggerate the health risks associated with bidi smoke. The burden of tobacco use is shifting from developed to developing countries and it is generally believed that smoking habit is on the rise in India [5, 12]. Therefore, the prevalence of COPD is expected to increase in the years to come and AE-COPD is likely to be an important reason for ER visits in India.
Clinical presentation of AE-COPD observed in the present study (Table 2) was similar to that reported from studies reported from other parts of the world [7, 13–18]. Several causes can contribute to altered sensorium in patients with AE-COPD. These include, type II respiratory failure and carbon dioxide narcosis, metabolic abnormalities such as dyselectrolytemia, uremia and hepatic function derangement among others. As these can be corrected, an active attempt must be made to identify them when patients present to the ER with AE-COPD. This is important in developing countries like India because, majority of the patients with AE-COPD seek emergency care at primary health centres, district hospitals and general hospitals where facilities for round-the-clock laboratory monitoring are seldom available. Unless these factors, that are often correctable, are specifically sought and checked, they may be missed. Thus, these factors not only confuse the diagnosis but also contribute to mortality.
Majority of the patients in the present study had co-morbid conditions (n = 53; 45.7%) (Table 1) and presence of co-morbid factors was a predictor of death (Table 5) in these patients. Co-morbid conditions can be a confusing factor when assessing a patient with AE-COPD, as they themselves can cause respiratory symptoms . Furthermore, the co-morbid conditions can trigger AE-COPD and their presence has been considered to be a predictor of poor outcome in several studies . In the present study, patients who presented with AE-COPD who also had type II diabetes mellitus and diabetic ketoacidosis (n = 3); type II diabetes mellitus and active pulmonary TB (n = 5) died suggesting that complications related co-morbid conditions also contribute to the morbidity and mortality. Therefore, accurate assessment of co-morbid conditions and institution of specific treatment aimed against them should also help in reducing the mortality in patients with AE-COPD.
In the present study, compared with those who did not develop AE-COPD, past history of pulmonary TB was more frequently documented in patients presenting to the ER with AE-COPD (p < 0.001). Furthermore, 28.4% patients with AE-COPD admitted to the medical ICU had evidence of past pulmonary TB and all males among them were chronic smokers (Table 1). In a survey of 60000 men aged 20 to 50 years , a definite correlation between the incidence of pulmonary TB and smoking has been documented. Gajalakshmi et al  observed that, among urban men, the death rates from medical causes of ever smokers were double those of never smokers. Of this excess mortality among smokers, a third involved respiratory disease, chiefly TB (risk ratio ever to never smoked = 4.5) suggesting that smoking per se increased the incidence of clinical TB. It has been suggested that nicotine turns off the production of tumor necrosis factor-alpha (TNF-α) by the macrophages in the lungs, and since TNF-α is crucial for the maintenance of the latent state within macrophages, reactivation may occur rendering the patient more susceptible to the development of progressive disease from latent M. tuberculosis infection . Treated pulmonary TB is an important cause of COPD  and has been reported in 41%  to 68%  patients treated for pulmonary TB. Smoking seems to increase the incidence of TB and prevalence of COPD is high where smoking is highly prevalent,. Cavitation, extensive fibrosis, bulla formation and bronchiectasis have been implicated in the genesis of COPD caused by destroyed lung due to treated pulmonary TB. Thus, in areas such as India where pulmonary TB is highly endemic and smoking is on the rise, the prevalence of COPD is expected to increase and severe AE-COPD would become a significant cause of morbidity and mortality in the ER. This intriguing relationship between smoking, pulmonary TB and COPD merits further study.
Five patients presenting with AE-COPD had type II diabetes mellitus and sputum smear-positive pulmonary TB. In the studies published from the west, there are scant references to active pulmonary TB as an infective cause of AE-COPD at the time of presentation to the ER [7, 13–18, 26]. This observation is particularly relevant to countries where TB is highly endemic. Patients with open TB in whom the diagnosis of TB is not considered due to low threshold of suspicion constitute a health hazard not only to the treating physicians in the ER, but also to the nursing and paramedical personnel. These observations merit further evaluation.
Lack of uniform definition of AE-COPD hampers international comparisons and the evolution of uniform diagnostic testing and treatment guidelines . Furthermore, initial evaluation of a patient in the ER in the guidelines issued by several international organisations are also different [27, 28]. The recently published Indian guidelines deal with AE-COPD only briefly . Guidelines for the initial diagnostic evaluation of AE-COPD should facilitate differentiating AE-COPD from other conditions which can mimick it such as congestive heart failure, pneumothorax, pleural effusion, pulmonary embolism and arrhythmias. With the evolution of a consensus definition , these differences are likely to be resolved.
Several studies have attempted to identify the predictors of poor outcome in patients with AE-COPD [7, 13–18, 26]. However, there has been no such study published from India to the best of our knowledge. Acute respiratory failure is a common reason for admission into the ICU in patients with AE-COPD [7, 13–18, 26]. We also observed that need for mechanical ventilation was associated with a poor prognosis (Table 5). The study was carried out at our tertiary care teaching institute with facilities for invasive monitoring and assisted mechanical ventilation. These facilities are not widely available and affordable in most of the Rayalaseema area of Andhra Pradesh and majority of patients needing assisted ventilation are referred here often, late in the course of their disease. This could be the reason for reason for the high prevalence of respiratory failure in these patients. In order to cope up with the expected increase in the burden of AE-COPD, there is a pressing need for making tertiary care facilities widely available and affordable in developing countries like India.
In conclusion, in addition to the host genetic factors genetic factors, smoking behaviour, accessibility to health care and presence of co-morbid conditions contribute to morbidity and mortality due to AE-COPD. Correction of metabolic abnormalities such as dyselectrolytemia and judicious use of empirical antimicrobial treatment will also help in reducing the mortality. Large scale nationwide multicentric studies are required to clarify these issues and evolve consensus guidelines. Further research is required to clarify the association between pulmonary TB and COPD.