Asthma and chronic obstructive pulmonary disease: are they the same or are they distinct diseases?
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Asthma↗
Biomedical subjects
Sunil K Chhabra
Publications and source records attributed to Sunil K Chhabra.
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.
Acute Disease↗
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 DeltaFEV1>or=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 (DeltaFEV1% predicted >or=9% and DeltaFEV1 of >or= 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.
Administration, Inhalation↗
Diagnosing tubercular pleural effusions.
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Adenosine Deaminase↗
Increased oxidative stress and altered levels of antioxidants in asthma.
BACKGROUND: Reactive oxygen species might play an important role in the modulation of airway inflammation. There is evidence of an oxidant-antioxidant imbalance in asthma. Although several oxidants and antioxidants are likely to be involved, alterations in only limited parameters have been studied in isolation. OBJECTIVE: We investigated changes in a wide range of oxidants and antioxidants to create a comprehensive picture of oxidant-antioxidant imbalance. METHODS: In the peripheral blood of 38 patients with bronchial asthma and 23 control subjects, oxidative stress was measured in terms of superoxide anion generation by leukocytes, lipid peroxidation products, total nitrates and nitrites, total protein carbonyls, and total protein sulfhydrils in plasma. Antioxidant status was evaluated by measuring red blood cell superoxide dismutase and catalase activity, total blood glutathione, and glutathione peroxidase activity in red blood cells and leukocytes and total antioxidant capacity in plasma. RESULTS: Asthmatic patients showed increased superoxide generation from leukocytes, increased total nitrites and nitrates, increased protein carbonyls, and increased lipid peroxidation products and decreased protein sulfhydrils in plasma, indicating increased oxidative stress. They also showed increased superoxide dismutase activity in red blood cells and increased total blood glutathione and decreased glutathione peroxidase activity in red blood cells and leukocytes. Red blood cell catalase activity and the total antioxidant capacity of plasma were not altered. CONCLUSION: There are alterations in a wide array of oxidants and antioxidants, with balance shifting toward increased oxidative stress in asthma. Therapeutic augmentation of the antioxidant defenses might be beneficial.
Adolescent↗
A study on the serum levels of interleukin-1beta in bronchial asthma.
Mononuclear phagocytes can be activated through an immunoglobulin E (IgE)- specific mechanism to release pro-inflammatory cytokine like interleukin-1beta (IL-1beta). The present study was conducted to show the inter-relationship between these two parameters in the serum of asthmatic patients. The study included 30 patients of asthma and 10 as control. Out of these 30 cases, 20 patients had stable and 10 had acute asthma. Of the 20 stable patients, 9 were allergic and 11 were non-allergic to either of the 12 allergens used for skin prick test. Serum IgE and IL-1beta levels were measured by enzyme linked immunosorbent assay (ELISA). Total serum IgE levels increased significantly (p < 0.05) in asthma [200.5 +/- 30.91 IU/ml, mean +/- standard error of mean (SEM)] in comparison with the controls (18.15 +/- 4.35 IU/ml). Serum IL-1beta level was higher in allergic (1.94 +/- 0.63 pg/ml) than in non-allergic patients (0.64 +/- 0.21 pg/ml) but it was not statistically significant (p > 0.05). The study suggests involvement of IgE and IL-1beta in the pathophysiology of allergic asthmatic condition. Further studies are required to delineate the inflammatory pathway in asthma and determine stages at which therapeutic interventions can be done.
Acute Disease↗
Comparison of acute bronchodilator effects of inhaled ipratropium bromide and salbutamol in bronchial asthma.
Both salbutamol (sal) and ipratropium (ipra) are effective bronchodilators in asthma patients. However, the issue of their relative status remains unresolved and the clinical factors affecting the responses have also not been adequately defined. The two drugs were compared in 44 asthmatics in a double-blind, randomized crossover, placebo-controlled study. There were four test days on which each patient received the following sequences of drugs: sal-sal-ipra, sal-sal-placebo, ipra-ipra-sal, and ipra-ipra-placebo. Baseline forced expiratory volume in 1 sec (FEV1) was similar on the four days. The change in FEV1 produced by salbutamol when given as the first bronchodilator was 0.50 +/- 0.30 L as compared to a change of 0.39 +/- 0.27 L produced by ipratropium (p < 0.01). Both salbutamol and ipratropium resulted in statistically similar further improvements in FEV1 when given as the second drug. There was, however, a wide patient-to-patient variability in response, with some patients showing greater improvement with salbutamol and others with ipratropium. Younger patients showed a greater response to salbutamol as compared to older patients, while no such difference was observed with ipratropium. Males responded better to both the drugs as compared to females. It was concluded that both salbutamol and ipratropium are effective bronchodilators in asthma patients, although the overall response to salbutamol appears to be superior. However, some patients may respond better to one or other of the two drugs. Sequential administration of the two drugs may be a justified therapeutic approach as some patients show have further improvement with use of the second drug.
Administration, Inhalation↗
Basis of rise in intracellular sodium in airway hyperresponsiveness and asthma.
The aim of this study was to investigate the basis of disturbances in sodium transport in asthma and in airway hyperresponsiveness without symptoms of asthma (asymptomatic AHR). We measured the intracellular sodium (Na(i)); activity of Na(+)/K(+)-ATPase in unstimulated cells (resting activity) and in cell homogenate under optimal conditions (maximal activity); and sodium influx, in mixed leukocytes of 15 normal subjects, 12 subjects with asymptomatic AHR, and 26 asthmatics with or without active symptoms. Resting Na(+)/K(+)-ATPase activity was the same as sodium influx, consistent with homeostasis. Compared with normal subjects, those with asymptomatic AHR or asthma with controlled symptoms had a twofold increase in sodium influx and Na(i). Symptomatic asthmatics also had a twofold increase in sodium influx but a fourfold elevation of Na(i). Maximal Na(+)/K(+)-ATPase activity was reduced by half in symptomatic asthmatics compared with normal subjects. The reduction of maximal Na(+)/K(+)-ATPase activity was associated with a significant decrease in ATP turnover per Na(+)/K(+)-ATPase molecule but not number of Na(+)/K(+)-ATPase molecules per cell. In summary, airway hyperresponsiveness with or without asthma is associated with increased sodium influx and Na in leukocytes. Resting activity of Na(+)/K(+)-ATPase is also increased as a compensatory response to the increased sodium influx, but it is achieved at the expense of higher Na(i). Symptomatic asthma is additionally associated with reduction in maximal activity of Na(+)/K(+)-ATPase, resulting in reduced capacity to handle the increase in sodium influx and consequent severe elevations in Na(i).
Asthma↗
Comparison of bronchodilator responsiveness in asthma and chronic obstructive pulmonary disease.
While asthmatics are known to have a greater response to bronchodilators than patients of chronic obstructive pulmonary disease (COPD), whether the pattern of response also differs has not been explored. Forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1) were measured before and 20 minutes after inhalation of 200 microg salbutamol in patients of bronchial asthma (n=133) and (COPD) (n=116). Three types of responses (defined as > or = 12% and 200 ml increase in FEV1 or FVC) were identified: increase in (i) only FVC (FVC response), (ii) only FEV1 (FEV1 response), and, (iii) both FVC and FEV1 (double response). The mean +/- SEM absolute increase in FEV1 was significantly greater in asthmatics (307+/-17ml) as compared to 120+/-12 ml in COPD patients (p<0.0001). On the other hand, the increase in FVC was not different in the two groups (296+/-22 ml and 230+/-24 ml, respectively, p>0.05). The proportion of subjects showing a > or = 200 ml increase in FEV1 was greater among asthmatics as compared to COPD (p<0.0001) but the proportions showing a > or = 200 ml in FVC were similar (p>0.05). All the three types of responses were observed in asthmatics with a double response being the commonest. In COPD, an FVC response was the predominant response while the FEV1 response was rare. Multinomial logistic regression revealed that younger subjects (below 45 years) were more likely to have a double or exclusive FEV1 response. Greater severity of obstruction was associated with higher odds for each of the three responses, the odds being especially very high for an exclusive FEV1 response. The odds for a double response and an exclusive FEV1 response were significantly increased in asthmatics as compared to COPD. For FVC response, age category and disease were not significant determinants. It was concluded that bronchodilator responsiveness in asthma and COPD differs not only quantitatively but also in the pattern.
Adult↗
An evaluation of salmeterol in the treatment of chronic obstructive pulmonary diseases.
BACKGROUND: Salmeterol has been shown a useful drug for the treatment of chronic obstructive pulmonary disease (COPD). However, its positioning in the current treatment of COPD remains to be defined. The present study was carried out to evaluate its role as an add-on drug to the current first-line drug, ipratropium. METHODS: A double-blind randomized, parallel group, placebo-controlled design was used in an outpatient setting. Thirty-three patients with moderate or severe COPD were included. After a run-in period of two weeks on 40 microg four-times-daily ipratropium and 400 microg twice-daily beclomethasone dipropionate, they were randomized into two groups to receive either salmeterol (50 microg twice daily) or placebo for eight weeks. The outcome parameters were: (i) spirometry, (ii) six-minute walking test, (iii) SF-36 health-related quality of life (HRQoL) questionnaire score, (iv) baseline dyspnoea index (BDI), (v) patient's self-assessment and (vi) supplemental use of salbutamol. RESULTS: The mean FEV1 and FVC increased significantly over the initial values in the salmeterol group but not in the placebo group. Salmeterol produced greater improvements in almost all the dimensions of HRQoL as well as in the BDI and the supplemental use of salbutamol was lower in this group. However, the six-minute walk distance was similar in the two groups. CONCLUSIONS: The present study shows that eight weeks treatment with salmeterol 50 microg twice-daily added to the existing regimen of ipratropium bromide and beclomethasone dipropionate provides greater symptomatic relief and improvement in lung function than placebo. This is accompanied by an improvement in the health-related quality of life.
Adult↗
Clinical significance of hilar thoracic index and width of right descending branch of pulmonary artery in chronic obstructive pulmonary disease.
BACKGROUND: Clinical recognition of pulmonary artery hypertension (PAH) is a major challenge in the management of COPD. Increased hilar-thoracic (HT) index and width of the descending branch of the right pulmonary artery (DRPA) measured on a plain PA chest radiograph have been shown to have a good correlation with pulmonary arterial pressures (PAP) measured by right-heart catheterization. Color Doppler echocardiography has evolved as a noninvasive method to estimate PAP. In the absence of information of the relationship between these radiological signs and PAP measured using this technique, we carried out the present study from an out patient unit of a tertiary care hospital. METHODS: Spirometry, arterial blood gas analysis and color Doppler echocardiography to estimate systolic and mean PAP were carried out in fifty patients with COPD. HT index and width of the DRPA were measured on a plain PA chest radiograph. RESULTS: The mean values and the proportions of patients with increased HT index (> 35%) and increased width of the DRPA (20 mm or more) increased with increasing severity of the disease. Both the indices had significant correlations with FEV1% predicted, arterial PO2, arterial PCO2 and the systolic pulmonary artery pressure, and, in the case of the HT index, also with the mean pulmonary arterial pressure. The two radiological indices were highly correlated with each other. Increased HT index and increased width of the DRPA had a 100% specificity and predictive value positive (PVP) in identifying patients with pulmonary hypertension. However, sensitivity and predictive value negative (PVN) were low. CONCLUSION: It was concluded that the HT index and width of the DRPA are useful and clinically valid measurements in patients with COPD.
Blood Pressure↗
Validation of the asthma quality of life questionnaire (AQLQ-UK English version) in Indian asthmatic subjects.
BACKGROUND: The Asthma Quality of Life Questionnaire (AQLQ) has been shown to have strong measurement properties. Quality of life instruments need to be validated under local conditions before these can be accepted for application in that community. The AQLQ has not been formally validated in India. OBJECTIVES: To measure the evaluative and discriminative properties of the AQLQ (UK English version) in Indian asthmatics. METHODOLOGY: Thirty-eight adult patients with asthma underwent spirometry and completed the AQLQ and the Asthma Control Questionnaire (ACQ), administered by an interviewer. Standard treatment was given for four weeks during which daytime and nocturnal symptoms of asthma, and use of rescue medication were recorded in diaries. The questionnaires were administered again at the end of four weeks and spirometry was repeated. RESULTS: The total and domain-wise scores of AQLQ improved in patients whose control of asthma improved during treatment. It had good reproducibility with no changes in scores in patients whose condition remained stable, and also high intraclass correlation coefficients for the total and domain-wise scores in these patients. Significant correlations were found between the changes in AQLQ scores and in ACQ scores confirming the longitudinal construct validity. The symptoms domain score of the AQLQ was related significantly to the patient diary-recorded scores of cough, sputum and nocturnal asthma. Cross-sectional construct validity of AQLQ was established by demonstrating significant correlation of total, and symptoms and emotions domain scores with the ACQ scores. CONCLUSIONS: It was concluded that the AQLQ (UK English version) has sufficiently acceptable evaluative and discriminatory properties in Indian subjects and is therefore a valid instrument for quality of life measurements in clinical and research studies in asthmatics in Indian patients.
Adult↗