Prediction Equations for Spirometry for Children from Northern India.

Objective: To develop prediction equations for spirometry for children from northern India using current international guidelines for standardization. Design: Re-analysis of cross-sectional data from a single school. Participants: 670 normal children (age 6-17 y; 365 boys) of northern Indian parentage. Methods: After screening for normal health, we carried out spirometry with recommended quality assurance according to current guidelines. We developed linear and nonlinear prediction equations using multiple regression analysis. We selected the final models on the basis of the highest coefficient of multiple determination (R2) and statistical validity. Main outcome measures: Spirometry parameters: FVC, FEV1, PEFR, FEF50, FEF75 and FEF25-75. Results: The equations for the main parameters were as follows: Boys, Ln FVC = -1.687+0.016*height +0.022*age; Ln FEV1 = -1.748+0.015*height+0.031*age. Girls, Ln FVC = -9.989 +(2.018*Ln(height)) + (0.324*Ln(age)); Ln FEV1 = -10.055 +(1.990*Ln(height))+(0.358*Ln(age)). Nonlinear regression yielded substantially greater R2 values compared to linear models except for FEF50 for girls. Height and age were found to be the significant explanatory variables for all parameters on multiple regression with weight making no significant contribution. Conclusions: We developed prediction equations for spirometry for children from northern India. Nonlinear equations were superior to linear equations.

Acute exacerbations of chronic obstructive pulmonary disease causes and impacts.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are recognised clinically as episodes of increased breathlessness and productive cough requiring a more intensive treatment. A subset of patients with this disease is especially prone to such exacerbations. These patients are labelled as ‘frequent exacerbators’. Though yet poorly characterised in terms of host characteristics, including any genetic basis, these patients are believed to represent a distinct phenotype as they have a different natural history with a more progressive disease and a poorer prognosis than those who get exacerbations infrequently. Most exacerbations appear to be associated with infective triggers, either bacterial or viral, although ‘non-infective’ agents, such as air pollution and other irritants may also be important. Susceptibility to exacerbations is determined by multiple factors. Several risk factors have been identified, some of which are modifiable. Chronic obstructive pulmonary disease (COPD) exacerbations are major drivers of health status and patient-centered outcomes, and are a major reason for health care utilisation including hospitalisations and intensive care admissions. These are associated with considerable morbidity and mortality, both immediate and long-term. These episodes have a negative impact on the patient and the disease including high economic burden, increased mortality, worsening of health status, limitation of activity, and aggravation of comorbidities including cardiovascular disease, osteoporosis and neuro-psychiatric complications. Exacerbations also increase the rate of progression of disease, increasing the annual decline in lung function and leading to a poorer prognosis. Evaluation of risk of exacerbations is now included as a major component of the initial assessment of a patient with COPD in addition to the traditionally used lung function parameter, forced expiratory volume in one second (FEV1). Decreasing the risk of exacerbations and their prevention is a major therapeutic goal of management in COPD.

Effect of patient education and standard treatment guidelines on asthma control: an intervention trial

Background: Denial of having a chronic condition, poor knowledge of the disease process and lack of adherence to standard treatment are often considered to be important factors that increase morbidity in asthma. We evaluated the effect of standard treatment guidelines and asthma education programme on asthma control among patients enrolled from a referral health facility of Delhi in India. Methods: Fifty patients who visited the health facility first time for treatment of asthma were enrolled after confirming the diagnosis of asthma by symptoms and reversible spirometry. Patients were interviewed at baseline using three researcher-administered questionnaires - quality of asthma management questionnaire, asthma control questionnaire (ACQ) and asthma knowledge questionnaire (AKQ). All patients were given pharmacotherapy according to standard treatment guidelines. In addition, every alternate patient was also given a face-to-face educational intervention. Patients were followed up at 2, 4, 8 and 12 weeks. The ACQ was used at each visit, and AKQ was reassessed at the twelfth week. The paired t test was used to detect significant changes in various domains of asthma control. Results: The knowledge of asthma among patients and the care provided by previous health-care providers were found to be poor at baseline assessment. The application of standard treatment guidelines improved asthma control by the second week and the changes became significant by the fourth week, which persisted till the twelfth week (p <0.0001). Educational intervention led to improvements in knowledge in several domains. Improvements in asthma symptoms began earlier among those who had additional educational intervention. Conclusions: Standard treatment guidelines and asthma education improved asthma control.

Exhaled breath condensate analysis in chronic obstructive pulmonary disease.

The increasing focus on airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) has led to development and evolution of tools to measure it. Direct assessment of airway inflammation requires invasive procedures, and hence, has obvious limitations. Non-invasive methods to sample airway secretions and fluids offer exciting prospects. Analysis of exhaled breath condensate (EBC) is rapidly emerging as a novel non-invasive approach for sampling airway epithelial lining fluid and offers a convenient tool to provide biomarkers of inflammation. It has definite advantages that make it an attractive and a feasible option. It is a source of mediators and molecules that are the causes or consequences of the inflammatory process. Measurement of such markers is increasingly being explored for studying airway inflammation qualitatively and quantitatively in research studies and for potential clinical applications. These biomarkers also have the potential to develop into powerful research tools in COPD for identifying various pathways of pathogenesis of COPD that may ultimately provide specific targets for therapeutic intervention. The EBC analysis is still an evolving noninvasive method for monitoring of inflammation and oxidative stress in the airways. The limited number of studies available on EBC analysis in COPD have provided useful information although definite clinical uses are yet to be defined. Evolving technologies of genomics, proteomics, and metabonomics may provide deeper and newer insights into the molecular mechanisms underlying the pathogenesis of COPD.

Coexistent chronic obstructive pulmonary disease-heart failure: Mechanisms, diagnostic and therapeutic dilemmas.

Mortality in chronic obstructive pulmonary disease (COPD) is more often due to cardiac rather than respiratory causes. The coexistence of heart failure (HF) and COPD is frequent but remains under-diagnosed. Both conditions share several similarities including the age of the population affected, a common risk factor in smoking and symptoms of exertional dyspnoea. There is also a strong possibility of COPD promoting atherosclerotic vascular disease through systemic inflammation. Both the conditions are punctuated by episodes of acute exacerbations of symptoms from time to time where differentiation between these two can be especially challenging. Although coexistence of the two is common, more often, only one of the two is diagnosed resulting in under-treatment and unsatisfactory response. Awareness of co-occurrence is essential among both pulmonologists and cardiologists and a high index of suspicion should be maintained. The coexistence of the COPD and HF also poses several challenges in management. Active search for the second disease using clinical examination supplemented with specialised investigations including plasma natriuretic peptides, lung function testing and echocardiography should be carried out followed by appropriate management. Issues such as adverse effects of drugs on cardiac or pulmonary function need to be sorted out by studies in coexistent COPD-HF patients. Caution is advised with use of β2-agonists in COPD when HF is also present, more so in acute exacerbations. On current evidence, the beneficial effects of selective β1-blockers should not be denied in stable patients who have coexistent COPD-HF. The prognosis of coexistent COPD and HF is poorer than that in either disease alone. A favourable response in the patient with coexistent COPD and HF depends on proper evaluation of the severity of each of the two and appropriate management with judicious use of medication.

Pulmonary hypertension associated with chronic obstructive pulmonary disease.

Pulmonary hypertension (PH) is likely to complicate chronic obstructive pulmonary disease (COPD) in a large proportion of patients, especially those with severe disease. Majority of patients have a mild to moderate elevation in the pulmonary artery pressure that usually does not require specific treatment. A small subset of patients, however, develops severe PH that is “out-of-proportion” to the severity of COPD. Generally considered a consequence of chronic hypoxaemia, endothelial dysfunction has now been recognised to play an important role in the pathogenesis of PH in COPD. Pulmonary vessels remodelling characterised by intimal enlargement with proliferating smooth muscle cells, medial hypertrophy, arteriolar muscularisation and endothelial cell proliferation, especially affecting the small arterioles and arteries, leads to permanent changes in the vascular structure and function. Clinical recognition of PH is difficult. Echocardiography is used for screening while right heart catheterisation is the gold standard for diagnosis. In patients who have a moderate degree of chronic hypoxaemia, long term oxygen therapy is indicated and is the only therapeutic measure so far known to retard the progress of PH. Newer therapies targeting the specific abnormalities of vasoconstrictor-vasodilator balance, arising as a consequence of endothelial dysfunction, are under investigation and may offer a management option especially in severe PH associated with COPD.

Allergic bronchopulmonary aspergillosis complicating childhood asthma.

While Allergic bronchopulmonary aspergillosis (ABPA) is known to complicate asthma in adults, its association with childhood asthma is very rare. We present two patients, a four-and half year old boy who presented with severe asthma and a 12 year-old girl whose previous chest radiographs revealed fleeting opacities. Both were diagnosed to be suffering from ABPA.

Regional variations in vital capacity in adult males in India: comparison of regression equations from four regions and impact on interpretation of spirometric data.

BACKGROUND: Information on variations in vital capacity predicted from various regional equations for adult males in India and on their impact on interpretation of spirometric data is not available. MATERIAL AND METHODS: In a retrospective study, spirometry data of 1672 male patients, aged 15 years and above were studied. Predicted values of forced vital capacity (FVC), labelled as FVC(North), FVC(East), FVC(West) and FVC(South) were calculated from the available regional prediction equations. A prediction equation for FVC for south Indian adults above 40 years of age is not available. Spirometry data was interpreted using these and the extent of agreement between pairs of equations in detection of pattern of abnormality was analysed. RESULTS: The FVC(North) and FVC(East) were close and greater than FVC(West) and FVC(South), which were in turn, close to each other. Up to the age of 40 years, the FVC(North) exceeded FVC(East), FVC(West) and FVC(South) by 2.4%, 11.8% and 13.3%, respectively, while in the above 40 years age group, it exceeded FVC(East) and FVC(West) by 5.1% and 9.67%, respectively. The differences, however, decreased substantially with increasing FVCs and even reversed at higher values with FVC(East) tending to exceed FVC(North) in both the age groups, and FVC(West) tending to exceed FVC(North) in the above 40 years age group. While northern and eastern, and, western and southern equations gave acceptable differences (less than 5%) in interpretation of abnormality in spirometric data in patients up to 40 years of age, differences between other pairs of equations in this age group, and between all pairs in the above 40 years age group were large and unacceptable. CONCLUSIONS: Substantial variations exist in vital capacity predicted from various regional equations in adult males in India. In general, northern and eastern equations, and, western and southern equations yield closer values. While the northern Indian equation gives the highest predicted vital capacity, this is true only for lower values of vital capacities and at higher values, this may be less than that predicted from eastern or western equations. The regional differences may result in unacceptable errors in interpretation of spirometry data, if inappropriate prediction equations are used.

Distribution and determinants of body mass index of non-smoking adults in Delhi, India.

Data on height and weight of 3,428 non-smoking healthy adult subjects, obtained during an earlier community-based study in Delhi, India, on chronic respiratory morbidity due to ambient air pollution was analyzed to study the distribution of body mass index (BMI) and its determinants among adults in Delhi. The sample was drawn by systematic sampling from rural and urban areas of Delhi. In urban areas, the sampling frame was restricted to areas around air quality-monitoring stations. However, the areas were spread across the city and reflected wide economic spectrum. Subjects were classified as underweight, normal, overweight, and obese as per the criteria of the World Health Organization for BMI. The mean BMI of the entire sample was 22.14 +/- 4.61. It was higher among females, urban residents, and the higher-income group. Overall, 49.7% of the 3,428 subjects had a normal nutritional status, 24.8% were underweight, 19.4% overweight, and 6.1% obese. The prevalence of underweight was higher in rural areas (38.5%) and among the lower-income group (39.9%), while overweight and obesity were more common in urban residents (22.7% and 7.5% respectively), among females (21.7% and 7.7%), and the higher-income group (31.8% and 11%) (p < 0.05). The adjusted odds for underweight were 2.02 for rural subjects and 4.00 for the lower-income group. For overweight or obesity, odds were 5.6 for the higher-income group, 3.62 for urban residents, and 2.5 for females. It was concluded that problems of both underweight and overweight and obesity exist among the adults of Delhi. While females, residents of urban areas, and economically-better-off were more likely to be overweight or obese, residents of rural areas and those from lower-income groups were more likely to be underweight.

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.

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.

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.

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.

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.