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Biomedical subjects

K Parameswaran

Publications and source records attributed to K Parameswaran.

At least 37 records · Page 2Linked to original sources
PubMed2000

Reproducibility, validity, and responsiveness of a disease-specific symptom questionnaire for gastroesophageal reflux disease.

The purpose of this study was to establish the reproducibility, validity, and responsiveness of a symptom questionnaire to assess patients with gastroesophageal reflux disease (GERD). A total of 300 patients with GERD completed questionnaires before and 6 months after laparoscopic Nissen fundoplication. Forty-six GERD patients who continued on omeprazole served as controls. Lower esophageal sphincter pressure, 24-h pH, and quality of life (SF36) were measured at baseline and follow-up. Reproducibility was calculated as an intraclass correlation coefficient (ICC) from a repeated-measures analysis of variance on symptom scores (SS) on two consecutive days. Validity was established by correlating SS with 24-h pH and SF36 scores. Responsiveness was calculated as the the ratio of the mean paired difference in score in the surgical group to the within-subject variability in control subjects. Reproducibility was very high, as revealed by an ICC of 0.92. Strong correlations between SS and SF36 scores at baseline and after surgery demonstrated high cross-sectional validity. Correlation between change in SS and change in pH, SF36 pain, general health, and physical health scores demonstrated longitudinal validity. The mean (95% confidence interval) paired differences in SS were 25.6 (23.7, 27.5) in the study and 2.0 (-3.2, 7.3) in the control groups, and the responsive index was 1.0. The estimated minimally important clinical difference was 7. We conclude that the symptom score is a reproducible, valid, and responsive instrument for assessing symptoms caused by GERD.

Anti-Ulcer Agents↗
PubMed2000

A comparison of exhaled nitric oxide and induced sputum as markers of airway inflammation.

BACKGROUND: Exhaled nitric oxide (ENO) has been proposed as a noninvasive marker of airway inflammation in asthma. OBJECTIVE: We investigated the relationships among ENO, eosinophilic airway inflammation as measured by induced sputum, and physiologic parameters of disease severity (spirometry and methacholine PC(20)). We also examined the effect of corticosteroid treatment and atopy on ENO levels and eosinophil counts in induced sputum. METHODS: Measurements were taken on one day in 22 healthy nonatopic subjects, 28 healthy atopic subjects, 38 asthmatic subjects not taking inhaled steroids, 35 asthmatic subjects taking inhaled steroids, and 8 subjects with eosinophilic bronchitis without asthma. RESULTS: ENO levels showed significant but weak correlations with eosinophil differential counts in the steroid-naive asthmatic and healthy atopic groups (r (s) < 0.05). ENO levels were significantly lower in the asthmatic subjects taking steroids compared with the asthmatic subjects not taking steroids, despite there being no difference in the sputum cell counts, and a tendency to increased airflow limitation. ENO levels and sputum eosinophil counts were equally good at differentiating from steroid-naive asthmatic subjects. ENO levels were consistently raised in subjects with eosinophilic bronchitis without asthma. Atopy had no effect on ENO levels in the healthy subjects. CONCLUSION: We conclude that ENO is likely to have limited utility as a surrogate clinical measurement for either the presence or severity of eosinophilic airway inflammation, except in steroid-naive subjects.

Administration, Inhalation↗
PubMed2000

Induced sputum cell counts in healthy adults.

Induced sputum cell counts provide a relatively noninvasive method to evaluate the presence, type, and degree of inflammation in the airways of the lungs. Their interpretation requires a knowledge of normal values from a healthy population. The objective was to examine the total and differential cell counts in induced sputum from a sample of healthy adults. A total of 118 healthy nonsmoking adults were studied. None had asthma or airflow obstruction (negative history, FEV(1) >/= 80% predicted, ratio of FEV(1) to vital capacity [FEV(1)/VC] >/= 80%, methacholine PC(20) >/= 16 mg/ml). Forty-six were atopic. Sputum induction produced an adequate sample in 96 subjects [53 males, mean age (range) 36 (18 to 60) yr]. The expectorate was processed within 2 h; sputum was selected, treated with dithiothreitol, filtered, and examined in a hemocytometer for total cell count and viability and on Wright-stained cytospins for a differential cell count. The mean, median (90th percentile) total cell count was 4.1, 2.4 (9.7) x 10(6) cells/g and cell viability was 69.6, 72.0 (89.7)%. The proportions of eosinophils were 0.4, 0.0 (1.1)%, neutrophils 37.5, 36.7 (64.0)%, macrophages 58.8, 60.8 (86.1)%, lymphocytes 1.0, 0.5 (2.6)%, metachromatic cells 0.0, 0.0 (0.04)%, and bronchial epithelial cells 1.6, 0.3 (4.4)%, respectively. Female gender and atopy were associated with a significant elevation of eosinophils; mean difference between male/female was 0.3% (p = 0.043) and between atopic/nonatopic 0.4% (p = 0.024). This study has identified reference values for total and differential cell counts in induced sputum of healthy adults.

Adolescent↗
PubMed1999

Concepts of establishing clinical bioequivalence of chlorofluorocarbon and hydrofluoroalkane beta-agonists.

There are no established guidelines for judging equivalence between inhaled medications. The principles of establishing bioequivalence on the basis of bioavailability and pharmacokinetics may not be applicable to inhaled medications with predominantly topical and minimal systemic effects. For inhaled beta(2)-agonists, the most practical method of showing in vivo therapeutic equivalence is by comparing relative potencies (RPs) of pharmacodynamic effects (bronchodilation and bronchoprotection). A range of doses that includes placebo should be studied in an appropriate design with adequate sample size, and relative potency should be estimated. Hydrofluoroalkane and chlorofluorocarbon salbutamol are bioequivalent for both their bronchodilator (RP, 1.08; 90% confidence interval, 0.95%, 1.23%) and bronchoprotective effects (RP, 1.08; 90% confidence interval, 0.81%, 1.46%) with similar safety profile. Eighteen subjects are required in a cross-over design to demonstrate bronchoprotective bioequivalence with a confidence interval of 67% to 150% for the relative potency (80% power). For salbutamol, this can be achieved with a comparison of 100 and 200 microgram doses. Twelve subjects would suffice for a cumulative dose-response study for bronchodilator bioequivalence. For both outcomes, repeatability and quality control of measurements have to be ensured for an accurate interpretation of the results.

Adrenergic beta-Agonists↗
PubMed1999

Acute effects of nebulised epoprostenol in pulmonary hypertension due to systemic sclerosis.

Pulmonary hypertension often has a lethal outcome in systemic sclerosis and the treatment is challenging. Epoprostenol is a potent pulmonary vasodilator and its efficacy has been demonstrated when delivered by the intravenous and aerosolized routes. We report the haemodynamic and functional benefits of epoprostenol administered by inhalation to a spontaneously breathing patient with partially reversible pulmonary hypertension due to systemic sclerosis. Aerosolized epoprostenol, equivalent to the maximum tolerated intravenous dose (31.2 micrograms), produced a 58% fall in pulmonary vascular resistance, increased the cardiac output by 42% and improved functional performance by one MET (3.5 ml kg-1 min-1 of oxygen uptake) without any significant side-effects. Selective distribution of epoprostenol by the inhaled route may offer a new strategy for treatment of pulmonary hypertension.

Administration, Inhalation↗
PubMed1999

Unusual radiological presentation and rapid fatal progression of invasive pulmonary aspergillosis in an immunocompetent young patient.

Invasive aspergillosis occurs very rarely in immunocompetent hosts. We describe a 21-year-old female with no obvious immunosuppression or underlying lung disease, who presented with minimal symptoms and bilateral hilar prominence on chest X-ray. Invasive aspergillosis was diagnosed on an open lung biopsy. She deteriorated in the ensuing 2 weeks and died of a sudden massive haemoptysis. This initial radiological abnormality and the rapid clinical course of the disease in young immunocompetent patients have not been previously reported.

Adult↗
PubMed1999

Predictors of asthma severity in the elderly: results of a community survey in Northeast England.

A number of risk factors for the development and severity of asthma in childhood are known. Particularly, there is information on allergens, excessive use of beta2- agonists, and indoor environmental pollutants. Similar information on elderly patients is lacking. We examined the risk factors for current asthma and for the severity of asthma in 95 elderly subjects (>65 years old) compared to 274 elderly subjects with obstructive spirometry who did not have asthma as defined by the following criteria: symptoms of episodic wheeze, cough, or chest tightness and forced expiratory volume in 1 sec/vital capacity (FEV1/VC) <70% with >15% or 200 mL reversibility in FEV1 to 200 microg salbutamol given from a metered-dose inhaler. The severity of airflow limitation was graded on the basis of the FEV1/VC ratio as mild (60%-70%), moderate (40%-60%), and severe (<40%). Asthma history was collected using the Medical Research Council respiratory questionnaire and a follow-up postal questionnaire. Data were analyzed using multiple logistic regression and the overall goodness-of-fit of the model was checked using the Hosmer-Lemeshow (HL) statistic. History of allergy (to one or more of the following allergens: cat, house dust, or grass or tree pollen) (odds ratio [OR] 25; 95% confidence interval [CI] 13-51; p = 0.0001) and history of childhood wheeze (OR 8; 95% CI 4-9; p = 0.004) were strong predictors of current asthma. Duration of wheezing, smoking history, indoor heating, history of working in coal mines, and sex were not predictors (HL 6.75, degrees of freedom [df] = 8, p = 0.56). Use of >4 puffs of salbutamol/ day (OR 5.3; 95% CI 2-14; p = 0.005), more than 10 years of asthma symptoms (OR 4.2; 95% CI 4.1-36.2; p = 0.0001), and >500 mL reversibility in FEV1 (OR 4.2; 95% CI 1.2-14.3; p = 0.05) were independent predictors of moderate to severe asthma. History of atopy was the strongest predictor of asthma in the elderly population studied. Indoor heating, presence of pets at home, sex, smoking history, and history of working in coal mines were not predictors of asthma. The severity of asthma as assessed by measurement of airflow limitation was related to the frequency of use of beta2-agonists, duration of symptoms of asthma, and increased reversibility of FEV1 to beta2-agonist.

Aged↗
PubMed1999

Use of peak flow variability and methacholine responsiveness in predicting changes from pre-test diagnosis of asthma.

Asthma is usually diagnosed clinically. This study investigated how methacholine challenge and peak expiratory flow monitoring influenced change from a pretest clinical diagnosis. Records of 132 patients referred with respiratory symptoms, who subsequently had reliable measurements of both airway responsiveness (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1 (PC20)) and peak expiratory flow variability (PEFV) were reviewed. Initial and final diagnoses for each patient were classified as: a) definite asthma; b) possible asthma; and c) definitely not asthma. The predictive value of PEFV and PC20 regarding overall change from pre- to post-test diagnosis, change from initial diagnosis of possible or definitely not asthma, and change from initial diagnosis of definite asthma, were tested by multiple logistic regression analysis. Odds ratios for PC20 were expressed per doubling dose, and for PEFV per 5% variability. Clinical diagnosis of definite asthma and definitely not asthma were confirmed in 70% and 79% respectively. PC20, but not PEFV, predicted an overall change between pre- and post-test diagnosis. Both PC20 and PEFV independently predicted change to definite asthma. PEFV and interaction between PC20 and PEFV predicted a change in those whose initial diagnosis was definite asthma. Although both measurements showed a significant correlation, there was poor agreement between positive tests. Both peak expiratory flow variability and provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second influence diagnostic decision-making in patients with a high pre-test probability of asthma.

Adult↗
PubMed1998

Asthma in the elderly: underperceived, underdiagnosed and undertreated; a community survey.

Bronchial asthma is now increasingly recognized in the elderly and is associated with significant morbidity and mortality. The aims of this study were two-fold: first, to assess the prevalence and, second, to evaluate diagnostic awareness, therapeutic management and patient perception of bronchial asthma among elderly patients in the community. From the age-sex register of an urban general practice in NE England, 2004 patients aged > 65 years were eligible for inclusion. Response to an initial screening questionnaire on respiratory symptomatology was 68% (n = 1362). Of these, 869 patients had respiratory symptoms: 390 voluntarily agreed to be evaluated further including assessment of airway physiology. In this group 369/390 had obstructive spirometry and, of these, 95 patients fulfilled clinical and physiological criteria of bronchial asthma. Prevalence of asthma within this age cohort was minimally and rather crudely assigned at 4.5% (95/2004). Among the 95 patients so-defined patients with asthma [age 70 +/- 8 years (mean +/- SD), FEV1 = 0.96 +/- 0.41, 33 male, 75 life-long non-smokers], subjective awareness, perception and attribution of pulmonary symptoms were poor. Further, despite tangible evidence of reversible and significant airflow limitation, only 21 were receiving inhaled glucocorticoid therapy (median daily dose 400 micrograms). Asthma in the elderly remains poorly perceived, poorly recognized and suboptimally treated. These findings are particularly apposite in the light of current epidemiological trends in asthma mortality and morbidity in elderly age cohorts.

Aged↗
PubMed1998

Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis.

A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment. Clinical measurements were made blind to the laboratory findings and vice-versa. Eighteen of 20 patients completed the study. Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia. Only in patients with sputum eosinophilia did prednisone, as compared with placebo, produce a statistically significant and clinically important mean effect on effort dyspnea of 0.8 (95% confidence interval [CI]: 0.3 to 1.2), p = 0.008, and in quality of life of 1.96 (95% CI: 0.5 to 3.3), p = 0.01, associated with a small improvement in FEV1 of 0.11 L (95% CI: - 0.04 to 0.23 L), p = 0.05. In these patients, prednisone also produced a significant decline in the median sputum eosinophil percentage, from 9.7% to 0.5% (p = 0.002), eosinophil cationic protein (ECP), from 6, 000 microgram/L to 1,140 microgram/L (p < 0.001), and fibrinogen, from 25. 3 mg/L to 5.4 mg/L (p < 0.001). These findings indicate that in smokers with severe airflow limitation, sputum eosinophilia predicts a beneficial effect of prednisone treatment. Improvement in FEV1, after prednisone treatment in this population, is small, and may not be appreciated in clinical practice.

Adult↗
PubMed1998

Serial sputum cell counts in the management of chronic airflow limitation.

This case study illustrates the usefulness of serial induced sputum cell counts from cytospins to investigate the nature of airway inflammation in a patient presumed to have prednisone-dependent asthma for 30 yrs. She had bronchiectasis and chronic airflow limitation. Exacerbations of breathlessness were associated with an increase in chronic airflow limitation with little or no sputum. Induced sputum showed elevated total cell and neutrophil counts at each exacerbation with no increase in the proportion of eosinophils. Pathogenic bacteria were cultured at each flare-up. The dose of prednisone was reduced progressively and each exacerbation was treated with an appropriate antibiotic without increasing the dose of prednisone, as was the case previously. The infections were associated with bronchiectasis of the right upper lobe which was removed. Examination of the specimen confirmed neutrophilic infiltration and did not show the usual airway structural changes of asthma. These results provide further evidence of the value of sputum cell counts in practice, in this case to prevent overtreatment with prednisone in a patient with recurrent deteriorations in airflow which were due to recurrent infections.

Asthma↗
PubMed1993

Concurrent catamenial hemothorax and hemopneumothorax.

We describe a case of catamenial hemothorax and hemopneumothorax occurring on both sides simultaneously; the patient responded remarkably with danazol therapy. To our knowledge, this is previously unreported in the literature.

Adult↗