Sunil K. Chhabra

Increased Oxidative Stress and Altered Levels of Antioxidants in Chronic Obstructive Pulmonary Disease

An imbalance between oxidative stress and antioxidative capacity has been proposed to play an important role in the development and progression of chronic obstructive pulmonary disease. We carried out a study to assess the systemic oxidant-antioxidant status in patients with chronic obstructive pulmonary disease (COPD) and relate it to the severity of disease. We measured a wide range of parameters of oxidant-antioxidant balance in leukocytes, plasma and red cells of 82 patients with COPD and 22 healthy non-smoking controls (HNC). Lung function was measured by spirometry. Staging of COPD was done as per the recommended guidelines. Red cell antioxidative enzyme activities were altered, with glutathione peroxidase (GSH-Px) having lower, superoxide dismutase (SOD) having greater and catalase having similar activity in patients as compared to HNC. In plasma, ferric reducing antioxidant power (FRAP) and total protein sulfhydryls were lower and GSH-Px, lipid peroxides measured as MDA-TBA products, and protein carbonyls were higher in the patients as compared to HNC. Plasma total nitrates and nitrites (NOx) were similar in the two groups. Superoxide anion (O2•−) release from leukocytes upon stimulation with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and total blood glutathione were also higher in patients as compared to HNC. Plasma FRAP had a positive whereas total blood glutathione had a significant negative correlation with the severity of airways obstruction (FEV1% predicted). Further, comparisons between clinical stages of severity of COPD revealed significant differences in plasma FRAP and total blood glutathione. Our observations suggest there is a systemic oxidant-antioxidant imbalance in the patients with COPD.

Ambient Air Pollution and Chronic Respiratory Morbidity in Delhi

Abstract The authors conducted a cross-sectional study among residents of Delhi to determine the role of ambient air pollution in chronic respiratory morbidity in Delhi. The authors selected a random, stratified sample (N = 4,171) of permanent residents who were 18+ y of age and who lived near 1 of the 9 permanent air quality monitoring stations in the city. Air-quality data for the past 10 y were obtained; data were based on the differences in total suspended particulates, and the study areas were categorized into lower- and higher-pollution zones. A standardized questionnaire was administered, clinical examination was carried out, and spirometry followed. The authors assessed chronic respiratory morbidity by (a) prevalence of chronic respiratory symptoms (i.e., chronic cough, phlegm, breathlessness, and wheezing) and airway diseases (i.e., chronic obstructive pulmonary disease/chronic bronchitis and bronchial asthma); and (b) lung function results in asymptomatic nonsmoking subjects in the two pollution zones. A multiple logistic regression identified the determinants of chronic symptoms. Smoking, male sex, increasing age, and lower socioeconomic status were strong independent risk factors for occurrence of chronic respiratory symptoms. In the comparison of nonsmoking residents of lower- and higher-pollution zones—stratified according to socioeconomic levels and sex—chronic cough, chronic phlegm, and dyspnea (but not wheezing) were significantly more common in the higher-pollution zone in only some of the strata. Furthermore, prevalence rates of bronchial asthma, chronic obstructive pulmonary disease, and chronic bronchitis among residents in the two pollution zones were not significantly different. Nonetheless, lung function of asymptomatic nonsmokers was consistently and significantly better among both male and female residents of the lower-pollution zone.

Increased Oxidative Stress in Acute Exacerbations of Asthma

Oxidant-antioxidant imbalance may play an important role in the pathogenesis of asthma, especially during acute exacerbations. To compare the systemic oxidant-antioxidant status in patients with acute exacerbations and stable asthma, we measured a wide range of parameters of oxidant-antioxidant balance in leukocytes, plasma, and red cells of 32 patients with acute exacerbations and 97 patients with stable asthma. These included measurement of superoxide anion generation by leukocytes, lipid peroxidation (measured as TBARS), total nitrates and nitrites, protein carbonyls, and protein sulfhydryls in plasma. Antioxidant status was evaluated by measuring the red cell superoxide dismutase and catalase activity, total blood glutathione, glutathione peroxidase activity in red cell and plasma, and total antioxidant capacity (assessed as ferric reducing antioxidant power) in plasma. Plasma total antioxidant capacity and total protein sulfhydryls were found to be decreased (p < 0.01), whereas plasma lipid peroxides were found to be increased (p < 0.05), in acute exacerbations of asthma. No significant differences were found in plasma glutathione peroxidase, protein carbonyls, and total nitrates and nitrites, red cell antioxidative enzyme activities, superoxide anion release from leukocytes, and total blood glutathione between the two groups (p > 0.05). Our observations suggest that acute exacerbations of asthma are associated with increased oxidative stress that is evident from some of the parameters in the plasma. Failure to observe simultaneous changes in all parameters of oxidative stress may be due to the possibility of their responses being dissociated in time or compensatory changes occurring in some of these.

Prevalence of Bronchial Asthma in Schoolchildren in Delhi

There is a paucity of information on the prevalence of asthma in children in India. Some evidence suggests that asthma is less common in developing than in the developed countries. The present study was carried out to estimate its current magnitude in children in Delhi. The questionnaire-based study was carried out in two randomly selected schools in Delhi. All the children were eligible. The age range was 4-17 years. The questionnaires were distributed to all the children present (n = 2867) to be answered by either parent. The key questions were related to complaints of recurrent wheezing in the past, in the last 1 year, and also wheezing exclusively induced by exercise or colds. In all, 2609 questionnaires were completed and returned (response rate 91%). There was a slight excess of males (54%). The prevalence of current asthma was 11.6% and past asthma was reported by 4.1% of children, giving a cumulative prevalence of 15.7%. Exclusive exercise-induced asthma was 2.8% and that associated with colds, 2.3%. The current prevalence of all wheezing was thus 16.7% and cumulative prevalence was 20.8%. While there was no sex-related difference in prevalence, wheezers were the highest in the 9-13 year age group. A significant association was found between the prevalence of wheezing and a family history of asthma (odds ratio 3.65) and presence of smokers in the family (odds ratio 1.62). When both the above factors combined, the odds ratio for risk of asthma was 4.58. There was no significant association with any economic class. Only 11% of asthmatics had been labeled so by their physicians. The prevalence of bronchial asthma and wheezing in children in Delhi is quite high and comparable to that reported from several developed countries. A positive family history of asthma and presence of smokers in the family emerged as significant risk factors.

Gender Differences in Perception of Dyspnea, Assessment of Control, and Quality of Life in Asthma

Background. There is limited information on the inter-relationship between gender, perception of dyspnoea and health-related quality of life (HRQoL) in asthma. Methods. In a cross-sectional study in an out-patient setting, 85 patients with bronchial asthma, 41 males and 44 females, underwent spirometry and were administered the following instruments to measure asthma control, HRQoL and dyspnoea : (a) Asthma control questionnaire (ACQ), (b) Asthma Quality of Life questionnaire (AQLQ), (c) Baseline dyspnoea index (BDI) questionnaire and Oxygen Cost Diagram (OCD). Results. Overall, male patients had greater airways obstruction but reported similar level of asthma control as females. Among patients with mild persistent asthma, females had a poorer level of control. The BDI and the OCD scores were significantly lower in female patients indicating greater dyspnoea and they also had a poorer quality of life especially in the symptoms and emotional domains of the AQLQ. After adjusting for the severity of airways obstruction in multivariate analysis, female gender and a poorer quality of life were independent predictors of increased perception of dyspnoea. Conclusions. Female patients with asthma are likely to have a greater perception of dyspnoea, report a poorer control and have a poorer quality of life as compared to males. Female gender and a poorer quality of life are independent predictors of increased perception of dyspnoea in asthmatics.

Risk factors for development of bronchial asthma in children in Delhi

BACKGROUND Information on the magnitude of the problem of childhood asthma in India and the factors influencing its occurrence is inadequate. OBJECTIVE To measure the prevalence of asthma in schoolchildren in Delhi and study the factors determining its occurrence. METHODS A questionnaire-based study carried out in nine randomly selected schools in Delhi. The age range was 5 to 17 years. The questionnaires were distributed to all the children (n = 21,367) for answering by either parent. The key questions relate to complaints of recurrent wheezing in the past, during the immediate last 1-year, and also wheezing exclusively induced by exercise or colds. In all, 19,456 questionnaires were received back (response rate 91%). Out of these, 18,955 were complete and analyzed. RESULTS The prevalence of current asthma was 11.9% while past asthma was reported by 3.4% of children. Exclusive exercise-induced asthma was reported by 2.1% while that associated with colds by 2.4% of children. Boys had a significantly higher prevalence of current asthma as compared with girls (12.8% and 10.7%, respectively). Multiple logistic regression analysis showed that male sex, a positive family history of atopic disorders, and the presence of smokers in the family were significant factors influencing the development of asthma while economic class, air pollution (total suspended particulates), and type of domestic kitchen fuel were not. CONCLUSIONS The prevalence of current asthma in children in Delhi is 11.9%. Significant risk factors for its development are male sex, a positive family history of atopic disorders, and the presence of smokers in the family.

Evaluation of three scales of dyspnea in chronic obstructive pulmonary disease

BACKGROUND: The Modified Medical Research Council (MMRC) scale, baseline dyspnea index (BDI) and the oxygen cost diagram (OCD) are widely used tools for evaluation of limitation of activities due to dyspnea in patients with chronic obstructive pulmonary disease (COPD). There is, however, limited information on how these relate with each other and with multiple parameters of physiological impairment. OBJECTIVES: To study the interrelationships between MMRC, BDI and OCD scales of dyspnea and their correlation with multiple measures of physiological impairment. MATERIALS AND METHODS: A retrospective analysis of pooled data of 88 male patients with COPD (GOLD stages II, III and IV) was carried out. Dyspnea was evaluated using the MMRC, BDI and OCD scales. Physiological impairment was assessed by spirometry (FVC % predicted and FEV1 % predicted), arterial blood gas (ABG) analysis and measurement of the 6-min walk distance (6MWD). RESULTS: The interrelationships between MMRC, BDI and OCD scales were moderately strong. The BDI and OCD scores had strong correlations with ABG abnormalities, weak correlations with spirometric parameters but none with 6MWD. MMRC grades were significantly associated with BDI and OCD scores but did not show clear associations with spirometric parameters, ABG abnormalities and 6MWD. CONCLUSIONS: The MMRC grades of dyspnea and the BDI and OCD scales are moderately interrelated. While the BDI and OCD scales have significant associations with parameters of physiological impairment, the MMRC scale does not.

Acute Bronchodilator Response Has Limited Value in Differentiating Bronchial Asthma from COPD

Background. Acute responsiveness to inhaled bronchodilators is often used to differentiate between bronchial asthma and chronic obstructive pulmonary disease (COPD). The response can be expressed in terms of a change in FEV1 and FVC in several ways—as absolute change, change as percent of baseline value, or as percent of predicted value with different thresholds for a positive test. A comprehensive evaluation of the diagnostic value of these different methods of expressing the acute bronchodilator response has not been carried out. Methodology. Response to inhaled salbutamol was measured by spirometry in 200 asthmatics and 154 patients with COPD. The sensitivity, specificity, and positive and negative predictive values of different methods of expressing responsiveness were calculated. Receiver operative characteristic curves were obtained. Results. None of the expressions of response gave a clear-cut separation between the two diseases. A ΔFEV1≥ 0.2 L gave the most satisfactory combination of sensitivity (73%) and specificity (80%) and the highest positive (82%) and negative predictive values (69%) for diagnosing asthma. These values were superior to those obtained for the ERS or the ATS criteria for reversibility (ΔFEV1%predicted ≥ 9% and ΔFEV1 of ≥ than 12% and 0.2 L over the baseline, respectively), which had almost similar diagnostic characteristics. This was confirmed by the area under curve of the ROC plots. Expressions of response in terms of changes in FVC were unsatisfactory in separating the two diseases. Conclusions. It was concluded that the test of acute bronchodilator responsiveness has limited diagnostic value in separating asthma and COPD.

Late Asthmatic Response in Exercise-Induced Asthma

BACKGROUND There is a controversy over the occurrence of a late asthmatic response during exercise-induced asthma. While some workers have documented such a response as a genuine phenomenon, others have attributed this to drug withdrawal. OBJECTIVES We carried out the present study to investigate whether a late asthmatic response occurs during exercise-induced asthma as a genuine event and, if so, what are the factors which determine its occurrence. METHODS Sixteen, clinically stable asthmatic patients with laboratory-proven exercise-induced asthma underwent a standardized exercise challenge on a bicycle ergometer. The airway response to exercise was studied by spirometry to measure FEV1. Spirometry was carried out before the exercise, at 4, 8, 15, 30, and 60 minutes, and then hourly for the next 7 hours. Spirometry was also done repeatedly as above on a non-exercise control day, four to seven days earlier. RESULTS Eight (50%) subjects developed a second fall of greater than 10% in FEV1, three to eight hours after recovery from the early response. The late fall in FEV1 after exercise was significantly greater than the spontaneous decay of lung function at the corresponding clocktime on the non-exercise control day. The dual responders did not differ from those with isolated early responses with respect to age, duration and severity of asthma, treatment requirements, peripheral blood eosinophilia, and atopic status. Baseline FEV1 and maximum fall in FEV1 during the early response, and the rate of its development and recovery from it were also similar. Among the dual responders, the late response was not related to the baseline FEV1 or to the intensity of the early response. CONCLUSIONS A late asthmatic response is a genuine phenomenon in exercise-induced asthma. Its occurrence cannot however be predicted by any clinical or physiologic factors.

Role of Mycoplasma pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease

Eighty per cent of the cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have an infective aetiology, atypical bacteria including Mycoplasma pneumoniae accounting for 5-10 % of these. However, the importance of association of M. pneumoniae with episodes of AECOPD still remains doubtful. The present study was therefore undertaken to delineate the extent of involvement of M. pneumoniae in patients with AECOPD at a referral hospital in Delhi, India. Sputum samples and throat swabs from a total of 100 AECOPD patients attending the Clinical Research Center of Vallabhbhai Patel Chest Institute, Delhi, were collected during a 2-year period (January 2004-June 2006). The samples were investigated for the presence of aerobic bacterial pathogens and M. pneumoniae. Diagnosis of infection with M. pneumoniae was based on culture, serology, direct detection of M. pneumoniae specific antigen and PCR. Bacterial aetiology could be established in 16 of the 100 samples studied. Pseudomonas spp. were recovered from eight cases, Streptococcus pneumoniae from four and Klebsiella spp. from two cases. Acinetobacter sp. and Moraxella catarrhalis were isolated from one case each. Serological evidence of M. pneumoniae infection and/or detection of M. pneumoniae specific antigen were seen in 16 % of the cases. One case with definite evidence of M. pneumoniae infection also had coinfection with Pseudomonas spp. However, no direct evidence of M. pneumoniae infection was found in our study population as defined by culture isolation or PCR. In conclusion, although the serological prevalence of M. pneumoniae infection in our study population was significantly higher than in the control group, there was no direct evidence of it playing a role in AECOPD.