Interpretation of Spirometry: Selection of Predicted Values and Defining Abnormality.

Spirometry is the most frequently performed investigation to evaluate pulmonary function. It provides clinically useful information on the mechanical properties of the lung and the thoracic cage and aids in taking management-related decisions in a wide spectrum of diseases and disorders. Few measurements in medicine are so dependent on factors related to equipment, operator and the patient. Good spirometry requires quality assured measurements and a systematic approach to interpretation. Standard guidelines on the technical aspects of equipment and their calibration as well as the test procedure have been developed and revised from time-to-time. Strict compliance with standardisation guidelines ensures quality control. Interpretation of spirometry data is based only on two basic measurements — the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) and their ratio, FEV1/FVC. A meaningful and clinically useful interpretation of the measured data requires a systematic approach and consideration of several important issues. Central to interpretation is the understanding of the development and application of prediction equations. Selection of prediction equations that are appropriate for the ethnic origin of the patient is vital to avoid erroneous interpretation. Defining abnormal values is a debatable but critical aspect of spirometry. A statistically valid definition of the lower limits of normal has been advocated as the better method over the more commonly used approach of defining abnormality as a fixed percentage of the predicted value. Spirometry rarely provides a specific diagnosis. Examination of the flow-volume curve and the measured data provides information to define patterns of ventilatory impairment. Spirometry must be interpreted in conjunction with clinical information including results of other investigations.

Prediction Equations for Spirometry in Adults from Northern India.

Background. Most of the Indian studies on prediction equations for spirometry in adults are several decades old and may have lost their utility as these were carried out with equipment and standardisation protocols that have since changed. Their validity is further questionable as the lung health of the population is likely to have changed over time. Objective. To develop prediction equations for spirometry in adults of north Indian origin using the 2005 American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations on standardisation. Methods. Normal healthy non-smoker subjects, both males and females, aged 18 years and above underwent spirometry using a non-heated Fleisch Pneumotach spirometer calibrated daily. The dataset was randomly divided into training (70%) and test (30%) sets and the former was used to develop the equations. These were validated on the test data set. Prediction equations were developed separately for males and females for forced vital capacity (FVC), forced expiratory volume in first second (FEV1), FEV1/FVC ratio, and instantaneous expiratory flow rates using multiple linear regression procedure with different transformations of dependent and/or independent variables to achieve the best-fitting models for the data. The equations were compared with the previous ones developed in the same population in the 1960s. Results. In all, 685 (489 males, 196 females) subjects performed spirometry that was technically acceptable and repeatable. All the spirometry parameters were significantly higher among males except the FEV1/FVC ratio that was significantly higher in females. Overall, age had a negative relationship with the spirometry parameters while height was positively correlated with each, except for the FEV1/FVC ratio that was related only to age. Weight was included in the models for FVC, forced expiratory flow (FEF75) and FEV1/FVC ratio in males, but its contribution was very small. Standard errors of estimate were provided to enable calculation of the lower limits of normal and standardised residuals for these parameters. The equations were found to be valid on the test dataset, and therefore, may be extended to general population. Comparison with the 1960s equations revealed lack of good agreement, and substantially higher predicted FVC with the current equations, especially in the forty-years-plus age group, in both males and females. Even in the age group upto 40 years, the level of agreement was clinically not acceptable. Conclusions. Validated prediction equations have been developed for spirometry variables in adults of north Indian origin using the current ATS/ERS spirometry standardisation recommendations. The equations suggest an improvement in the lung health of the population over time in the middle-aged and the elderly. These equations should address a long-felt unmet need and enable a more appropriate evaluation of spirometry data in different chest diseases in Indian subjects.

Quality of asthma management in an urban community in Delhi, India.

Background & objectives: High prevalence and poor control of asthma make its management a major public health issue worldwide, especially in developing countries. Optimum review of asthma management in the community is essential to improve asthma control. This study was conducted to investigate the quality of asthma management, knowledge about asthma and quality of life of asthma patients referred to a public tertiary care chest hospital in Delhi. Methods: Diagnosis of asthma was confirmed by symptoms and reversible spirometry in 50 referred patients on their first visit. Patients were interviewed using three questionnaires on quality of asthma management before visiting referral hospital, asthma knowledge and asthma quality of life (AQLQ). Correlation amongst quality of treatment, asthma quality of life, and asthma knowledge was also determined. Results: Findings revealed that only 60 per cent of patients were informed about their disease, and 10 per cent had undergone lung function tests previously. Only 44 per cent of patients were prescribed inhalers. None were provided with any educational material. Patients had poor knowledge of aetiology, pathophysiology, medication and how to assess the severity of their asthma. The mean scores in AQLQ indicated a moderate degree of impairment in quality of life. Interpretations & conclusions: This study provides evidence of unsatisfactory asthma management and patient-doctor interaction as patients had limited knowledge of asthma disease, its management and had poor quality of life as measured by a standardized questionnaire. Thus, there is need to implement suitable interventions to improve asthma management according to standard treatment guidelines in the community.

Regression equations for spirometry in children aged 6 to 17 years in Delhi region.

Background. Most of the studies carried out in India to develop regression equations for spirometry in children are now several years-to-decades old and had used equipment and measurement protocols that have since changed. Prediction equations using the current standardisation protocols for spirometry are not available. The lung health of the population may have changed too. Objective. To develop regression equations for spirometry for children aged 6 to 17 years of north Indian origin in Delhi region. Methods. School children of north Indian origin, as determined by mother tongue and parentage, aged 6 to 17 years were screened by a health questionnaire and physical examination and those found “normal” underwent spirometry according to the standardised procedure recommended by the American Thoracic Society/ European Respiratory Society (ATS/ERS) task force in 2005. Pearson’s correlation analysis was carried out to identify the predictor variables for spirometric parameters. Prediction equations were developed using the multiple linear regression procedure. The independent variables were entered in sequence of height, age and weight. R2, adjusted R2 and R2 change, standard errors of the estimate (SEE), and estimates of regression coefficients were obtained and the goodness of fit was examined. Results. Data was obtained in 365 boys and 305 girls. Forced vital capacity (FVC), forced expiratory volume in one second(FEV1), peak expiratory flow rate (PEFR), forced expiratory flow rate at 50% and 75% exhalation of vial capacity (F50 and F75) and mean forced expiratory flow rate over the middle 50% of the vital capacity (F25-75) showed moderate to strong correlations with age, height and weight in both boys and girls. In both genders, the equations explained very high variability of FVC, FEV1 and PEFR as shown by the R2 values. The explained variability for flow rates was lesser, with that for F75 being the least. Conclusions. Regression equations for spirometry variables for children of north Indian origin in Delhi region have been developed. These represent the first such effort from India after the publication of the ATS/ERS task force 2005 guidelines on standardisation of spirometry.

Effect of ozone on response to ovalbumin & its modulation by vitamins C & E in sensitized guinea pigs.

Background & objectives: Exposure to ozone and asthma are both associated with increased oxidative stress. Exposure to ozone therefore, may potentiate the airway response to allergens. We undertook this study to investigate the effect of ozone exposure on airway response to ovalbumin in sensitized guinea pigs and its modulation by dietary supplementation with antioxidant vitamins C and E. Methods: After in vivo measurements of specific airways conductance (SGaw) and airway hyperresponsiveness (AHR) to inhaled histamine, guinea pigs were sensitized to ovalbumin and divided into three groups: (i) sensitized; (ii) sensitized and exposed daily to ozone; and (iii) sensitized, exposed daily to ozone and given dietary supplementation with vitamin C, 2 mg/kg body wt and E, 7 IU/kg body wt. A control group of nonsensitized animals was included. After 4 wk, AHR was measured again and animals were challenged with inhaled ovalbumin. Changes in SGaw were followed for early and late airway bronchoconstrictive responses. The following measurements were obtained: (i) parameters of oxidative stress - plasma malonaldehyde (MDA) as marker of lipid peroxidation and superoxide anion generation by leukocytes and bronchoalveolar lavage (BAL) cells; (ii) antioxidant status: red cell superoxide dismutase (SOD); and (iii) glutathione peroxidase (GPx). BAL cytology was studied. Results: Ozone exposure resulted in an increase in AHR and early and late bronchoconstrictive responses after ovalbumin challenge, greater superoxide anion generation in BAL cells, higher plasma MDA levels and decrease in red cell SOD activity. Dietary supplementation with vitamin C and E prevented or ameliorated these responses. Interpretation & conclusions: Exposure to ozone at concentrations of 0.12 ppm for 2 h daily for 4 wk enhances the airway response to allergens in sensitized guinea pigs. Dietary supplementation with antioxidant vitamins E and C, affords variable degree of protection against this enhancement.

Effect of vitamin E supplementation with standard treatment on oxidant-antioxidant status in chronic obstructive pulmonary disease.

BACKGROUND & OBJECTIVES: Chronic oxidant burden and depletion of endogenous antioxidants have been proposed to play a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Exogenous antioxidants have potential therapeutic implications and their role has not been explored in COPD. The objective of this study was to investigate the effect of supplementation of standard treatment (inhaled long-acting beta(2) agonists, anticholinergics and corticosteroids) with vitamin E on oxidant-antioxidant balance in patients with COPD. METHODS: The study was carried out in the outpatient setting. Patients were divided into two groups: group A- placebo group (n=14), receiving only standard therapy, and group B- vitamin E-supplemented group (n=10), receiving 400 IU of vitamin E capsules twice daily in addition to standard therapy. Spirometry and clinical assessment were carried out at the start and completion of 8 wk treatment along with measurements of several biochemical parameters of oxidant-antioxidant status in plasma, leukocytes and red cells separated from venous blood. RESULTS: Leukocyte superoxide generation was decreased in both the groups. Vitamin E-supplemented group had significantly increased levels of plasma sulphydryls and red cell catalase while the placebo group had decreased levels of plasma nitrates and nitrites. No significant differences were observed in red cell superoxide dismutase and glutathione peroxidase activities, total blood glutathione, and plasma total antioxidant capacity, lipid peroxides and glutathione peroxidase activity in either group. There was a similar degree of lung function and clinical improvement in both the groups. INTERPRETATION & CONCLUSION: Our findings showed that an 8 wk supplementation of standard treatment with 400 IU twice daily of vitamin E did not provide any additional clinical benefit although it augmented certain endogenous antioxidants in patients with COPD.

Assessment of control in asthma: the new focus in management.

Several evidence-based guidelines on the management of asthma have been developed in the last two decades. There is a consensus that a stepped-up approach with anti-inflammatory drugs based on severity forms the cornerstone of treatment. Goals of management have been defined. Studies in several countries have however shown that a large majority of patients have failed to attain the goals of treatment. This has led to a reconsideration of strategy of management. The focus is now shifting to an assessment and a treatment approach based on control. The objective is to achieve and monitor to maintain control. The previous treatment algorithms based on assessment of severity are being discarded. It has been emphasised that the state of control is a dynamic one and therefore a regular assessment and modifications of treatment according to changes in its level are necessary. There is a need to use some method to assess control. A wide range of techniques to assess control are available that can be used depending on the requirements, settings and resources. Assessment of control may be an informal global judgement by the physician or simple tools may be used. Several formal instruments to assess the state of control have also been developed and validated in different settings. These allow a more objective and a quantitative evaluation. Control needs to be assessed at every visit of a patient and treatment adjusted accordingly.

Inhaled formoterol versus ipratropium bromide in chronic obstructive pulmonary disease.

BACKGROUND: Short-acting anticholinergic bronchodilator, ipratropium bromide has been recommended as first-line drug in chronic obstructive pulmonary disease (COPD). More recently, long acting beta2-agonist (LABA) bronchodilators such as formoterol have been shown to be useful in COPD. Limited information is available on the relative efficacy of these two drugs in COPD. METHODOLOGY: A randomised, double-blind, cross-over, placebo-controlled study was carried out. Forty-four stable patients with COPD received single doses of formoterol (12 microg), ipratropium bromide (40 microg) or placebo, administered through a metered-dose inhaler on three consecutive days in a random order. Spirometry, static lung volumes, pulse rate and blood pressure, and assessment of sensation of dyspnoea at rest using a visual analog scale (Borg Scale) were recorded at baseline. Subsequently, these were repeated for assessment of response: spirometry at 5, 30 and 60 minutes and static lung volumes, pulse rate, blood pressure and dyspnoea measurement at 60 minute. RESULTS: Formoterol resulted in greater immediate improvement in lung function, with the change in FEV1 at 5 min being greater than that observed with ipratropium. The changes in static lung volumes were similar between the two but superior to placebo. Both the drugs reduced dyspnoea. Formoterol produced a significantly greater increase in heart rate and systolic blood pressure as compared to ipratropium, although the magnitude of these changes was small and clinically unimportant. CONCLUSIONS: Single therapeutic doses of formoterol and ipratropium bromide are equally effective in improving lung function and reducing dyspnoea. However, formoterol appears to be a better bronchodilator producing a faster improvement in lung function.

Household environmental tobacco smoke exposure, respiratory symptoms and asthma in non-smoker adults: a multicentric population study from India.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is a risk factor for childhood asthma. Its association with asthma in adults is less clear. METHODS: In a multicentric population study on asthma prevalence in adults, specific enquiries were made into childhood and adulthood exposure to household ETS, and its relationship with asthma diagnosis were analysed. RESULTS: From a total of 73605 respondents, 62109 were studied after excluding current or past smokers. Overall observed prevalence of asthma was 2.0% (men 1.5%,women 2.5%, p < 0.001). Of all asthma patients, history of ETS exposure was available in 48.6 percent. Prevalence of asthma in the ETS exposed subjects was higher compared to non-exposed individuals (2.2% vs 1.9%, p < 0.05). Multiple logistic regression analysis showed a higher risk of having asthma in persons who were exposed to ETS compared to those not exposed (odds ratio [OR] 1.22, 95% CI 1.08-1.38) after adjusting for age, gender, usual residence, exposure to biomass fuels and atopy. Stratification of ETS exposure revealed that exposure during childhood and both during childhood and adulthood were significantly associated with asthma prevalence. Exposure only in adulthood was not a significant risk factor (OR 1.13, 95% CI 0.95-1.33). Persons reporting combined environmental tobacco smoke exposure from parents during childhood and spouse during adulthood had highest risk of having asthma (OR 1.69, 95% CI 1.38-2.07). Environmental tobacco smoke exposure was also significantly associated with prevalence of respiratory symptoms such as wheezing, cough and breathlessness. CONCLUSIONS: Environmental tobacco smoke exposure during childhood is an important risk factor for asthma and respiratory symptoms in non-smoking adults.

Tobacco smoking in India: prevalence, quit-rates and respiratory morbidity.

BACKGROUND: Population prevalence of tobacco smoking especially with reference to detailed habits such as the amount smoked, the smoking forms, quit-rates and relationship with demographic variables were studied at four different centres in India along with the study on epidemiology of asthma and chronic obstructive pulmonary disease. METHODS: The study population included adults of over 15 years of age selected with two-stage stratified random sample design. A specifically designed questionnaire was used for the study. RESULTS: There were 11496 (15.6%) ever smokers in the study sample of 73605 subjects. Among 37682 males, 10756 (28.5%) were ever smokers and among 35923 females, 740 (2.1%) were ever smokers. Bidi was the commonest form of smoking, more so in the rural areas. The mean number of cigarettes/bidis smoked per day was 14 (+/- 11.5) and the mean age of starting smoking was 20.5 (+/- 20.0) years. Increasing age, low socio-economic status and rural residence were important factors associated with smoking. Vigorous anti-tobacco measures under the tobacco control programmes yielded only a quit-rate of 10 percent. Nearly 14% of ever smokers had some respiratory symptoms. CONCLUSIONS: A substantial proportion of population in India has current or past smoking habit with higher prevalence among males than females. The quit-rates have been low in spite of the various anti-tobacco measures. There is a significant respiratory morbidity associated with smoking.

Prevalence and risk factors for bronchial asthma in Indian adults: a multicentre study.

BACKGROUND: There is limited information on field epidemiology of bronchial asthma in Indian adults. OBJECTIVES: To estimate prevalence of bronchial asthma in different regions of India and to define risk factors influencing disease prevalence. METHODS: A field study was conducted at Chandigarh, Delhi, Kanpur and Bangalore through a two stage stratified (urban/ rural) sampling and uniform methodology using a previously validated questionnaire. Asthma was diagnosed if the respondent answered affirmatively both to (a) whistling sound from chest, or chest tightness, or breathlessness in morning, and (b) having suffered from asthma, or having an attack of asthma in the past 12 months, or using bronchodilators. Besides demographic data, information on smoking habits, domestic cooking fuel used, atopic symptoms, and family history suggestive of asthma was also collected. Univariate and multivariate logistic regression modelling was performed to calculate odds ratio of various potential risk factors. RESULTS: Data from 73605 respondents (37682 men, 35923 women) were analysed. One or more respiratory symptoms were present in 4.3-10.5% subjects. Asthma was diagnosed in 2.28%, 1.69%, 2.05 and 3.47% respondents respectively at Chandigarh, Delhi, Kanpur and Bangalore, with overall prevalence of 2.38%. Female sex, advancing age, usual residence in urban area, lower socio-economic status, history suggestive of atopy, history of asthma in a first degree relative, and all forms of tobacco smoking were associated with significantly higher odds of having asthma. CONCLUSION: Prevalence estimates of asthma in adults in this study, although lower than several previously reported figures, point to a high overall national burden of disease.

A multicentric study on epidemiology of chronic obstructive pulmonary disease and its relationship with tobacco smoking and environmental tobacco smoke exposure.

INTRODUCTION: Population prevalence of chronic obstructive pulmonary disease (COPD) and its relationship with tobacco smoking, environmental tobacco smoke (ETS) exposure and other variables were studied in adult subjects of 35 years and above at four different centres in India. Question-items for the diagnosis of COPD were included in the questionnaire used for the field study on asthma epidemiology. METHODS: Field surveys were conducted in both the urban and the rural populations at Bangalore, Chandigarh, Delhi and Kanpur with the help of a structured and validated questionnaire for diagnosis of asthma and COPD. Separate sets of questions were used for the diagnoses of the two diseases. A two-stage stratified sample design was employed where a village or an urban locality formed the first stage unit and a household formed the second stage unit. A uniform methodology was used at all the four centres and the analyses were done at the central coordinating centre--Chandigarh. Chronic obstructive pulmonary disease, defined by chronic bronchitis (CB) criteria, was diagnosed from the presence of cough and expectoration on most of the days for at least three months in a year for two consecutive years or more. RESULTS: Chronic obstructive pulmonary disease was diagnosed in 4.1% of 35295 subjects, with a male to female ratio of 1.56:1 and a smoker to nonsmoker ratio of 2.65: 1. Prevalence among bidi and cigarette smokers was 8.2% and 5.9%, respectively. Odds ratio (OR) for COPD was higher for men, elderly individuals, lower socio-economic status and urban (or mixed) residence. Environmental tobacco smoke exposure among nonsmokers had an OR of 1.4(95% CI 1.21-1.61). Combined exposure to both ETS and solid fuel combustion had higher OR than for ETS exposure alone. CONCLUSIONS: Population prevalence of COPD is very high in India with some centre to centre differences. Smoking of both bidis and cigarettes, and ETS exposure among nonsmokers, were two important risk factors at all centres. It is important to employ uniform methodology for assessment of national burden and disease-surveillance programme.

Study on serum and urinary cortisol levels of asthmatic patients after treatment with high dose inhaled beclomethasone dipropionate or budesonide.

BACKGROUND: The potential for long-term adverse effects from inhaled corticosteroids relates to their systemic absorption. With increasing use of high dose inhaled corticosteroids, there is need to establish whether similar doses of beclomethasone dipropionate (BDP) and budesonide (BUD) produce clinically important differences in untoward side effects specially hypothalamo-pituitary-adrenal (HPA) axis suppression. METHODS: Fifteen asthmatic patients were started on BDP or BUD (2000 microg/day) through spacer for six weeks. Serum cortisol (9 AM and 4 PM), 24-hour urinary steroid and pulmonary function testing parameters were performed. RESULTS: The serum cortisol levels were not found to be suppressed with either BDP or BUD. Similarly no significant changes were found in 24 hours urinary excretion of steroids with either of the drugs. Significant improvement was found in values of forced expiratory volume in the first second (FEV1) with BDP. With BUD the changes in forced vital capacity (FVC) and FEV1 were found to be significant. CONCLUSION: BDP or BUD in high doses of 2000 microg/day given upto six weeks through spacer are equally effective for treatment of bronchial asthma and do not cause any significant change in serum and urinary cortisol levels, and adrenal function/HPA axis.

Premenstrual asthma.

Gender differences have been recognized in asthma. Specifically in women, an exacerbation in symptoms occurring a few days prior to the onset of menstruation constitutes a phenotype that is not yet fully understood. This phenomenon, called "premenstrual asthma," has been reported to affect upto 40% women with asthma. This article reviews the literature on prevalence, effect of menstrual cycle on symptoms and lung function and discusses the proposed mechanisms of pathogenesis including the effects of female sex hormones on symptoms and beta2 adrenergic receptor function, and the role of airway inflammation. Finally, the various treatment options are presented.