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Biomedical subjects

I D Pavord

Publications and source records attributed to I D Pavord.

At least 19 recordsLinked to original sources

A case of cough, lymphocytic bronchoalveolitis and coeliac disease with improvement following a gluten free diet.

Chronic cough is a common reason for presentation to a respiratory clinic. In up to 20% of cases the cause remains unclear after investigations. We report one such case where there was bronchoscopic evidence of lymphocytic airway inflammation in association with newly diagnosed coeliac disease. All features improved markedly on a gluten free diet, suggesting a causal relationship between coeliac disease, cough, and lymphocytic bronchoalveolitis.

Aged↗

Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants.

BACKGROUND: Despite having a work related deterioration in peak expiratory flow (PEF), many workers with occupational asthma show a low degree of within day diurnal variability atypical of non-occupational asthma. It was hypothesised that these workers would have a neutrophilic rather than an eosinophilic airway inflammatory response. METHODS: Thirty eight consecutive workers with occupational asthma induced by low molecular weight agents underwent sputum induction and assessment of airway physiology while still exposed at work. RESULTS: Only 14 (36.8%) of the 38 workers had sputum eosinophilia (>2.2%). Both eosinophilic and non-eosinophilic groups had sputum neutrophilia (mean (SD) 59.5 (19.6)% and 55.1 (18.8)%, respectively). The diurnal variation and magnitude of fall in PEF during work periods was not significantly different between workers with and without sputum eosinophilia. Those with eosinophilia had a lower forced expiratory volume in 1 second (FEV1; 61.4% v 83% predicted, mean difference 21.6, 95% confidence interval (CI) 9.2 to 34.1, p=0.001) and greater methacholine reactivity (geometric mean PD20 253 microg v 1401 microg, p=0.007). They also had greater bronchodilator reversibility (397 ml v 161 ml, mean difference 236, 95% CI of difference 84 to 389, p=0.003) which was unrelated to differences in baseline FEV(1). The presence of sputum eosinophilia did not relate to the causative agent, duration of exposure, atopy, or lack of treatment. CONCLUSIONS: Asthma caused by low molecular weight agents can be separated into eosinophilic and non-eosinophilic pathophysiological variants with the latter predominating. Both groups had evidence of sputum neutrophilia. Sputum eosinophilia was associated with more severe disease and greater bronchodilator reversibility but no difference in PEF response to work exposure.

Asthma↗

The relation between peripheral blood leukocyte counts and respiratory symptoms, atopy, lung function, and airway responsiveness in adults.

STUDY OBJECTIVES: Eosinophils and neutrophils play major roles, respectively, in the pathogenesis of asthma and COPD, and it is well recognized that levels of these cells in peripheral blood are increased in relation to their pulmonary involvement. However, the relation between peripheral blood cell counts of the other major leukocyte groups and these lung diseases or markers of allergy or airflow obstruction is less clear. We have therefore investigated the association between peripheral blood levels of eosinophils, neutrophils, basophils, monocytes, and lymphocytes and the occurrence of chronic respiratory symptoms, atopy, lung function, and bronchial hyperresponsiveness, and the modifying effect of age, in adults. DESIGN: A cross-sectional general population study. SETTING: Data on > 2,000 British adults, who originally participated in a study of diet and lung health, were analyzed using multiple linear and logistic regression to adjust for potential confounders, including age, sex, and smoking history. RESULTS: We found that, like eosinophils, the peripheral basophil count was increased in relation to asthma and associated symptoms, and to airway hyperreactivity and increased total IgE, but differed from eosinophils in that basophils were unrelated to atopy. Monocytes were predominantly associated with symptoms indicative of obstructive airway disease, in similar relation to neutrophils, but both of these leukocyte counts were also increased in asthma patients in older age groups. Lymphocyte counts were unrelated to any objective or subjective marker of disease. CONCLUSIONS: If peripheral blood cell counts reflect pulmonary involvement of these leukocyte groups, basophils and monocytes may play a distinct role in the pathogenesis of allergic and nonallergic respiratory disease.

Adolescent↗

Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: Some patients with chronic obstructive pulmonary disease (COPD) respond to corticosteroid therapy. Whether these patients have different airway pathology from other COPD patients is unclear. We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation. METHODS: We did a randomised, double-blind, crossover trial. Patients who had COPD treated with bronchodilators only were assigned placebo and 30 mg prednisolone daily for 2 weeks each, in a random order, separated by a 4-week washout period. Before and after each treatment period, we assessed patients with spirometry, symptom scores, the chronic respiratory disease questionnaire (CRQ), incremental shuttle walk test, and induced sputum. Analysis was done by intention to treat. FINDINGS: 83 patients were recruited, of whom 67 were randomised. The geometric mean sputum eosinophil count fell significantly after prednisolone (from 2.4% to 0.4%; mean difference six-fold [95% CI 3.1-11.4]) but not after placebo. Other sputum cell counts did not change. After stratification into tertiles by baseline eosinophil count, postbronchodilator forced expiratory volume in 1 s (FEV1) and total scores on the CRQ improved progressively after prednisolone from the lowest to the highest eosinophilic tertile, compared with placebo. The mean change in postbronchodilator FEV1, total CRQ score, and shuttle walk distance with prednisolone compared with placebo in the highest tertile was 0.19 L (0.06-0.32), 0.62 (0.31-0.93), and 20 m (5-35), respectively. INTERPRETATION: Our findings suggest that eosinophilic airway inflammation contributes to airflow obstruction and symptoms in some patients with COPD and that the short-term effects of prednisolone are due to modification of this feature of the inflammatory response. The possibility that sputum eosinophilia identifies a subgroup of patients who particularly respond to long-term treatment with inhaled corticosteroids should be investigated.

Adult↗

Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis.

Eosinophilic bronchitis is a common cause of chronic cough, characterized by sputum eosinophilia similar to that seen in asthma, but unlike asthma the patients have no objective evidence of variable airflow obstruction or airway hyperresponsiveness. The reason for the different functional associations is unclear. The authors have tested the hypothesis that in eosinophilic bronchitis the inflammation is mainly localized in the upper airway. In an open study the authors measured the lower (provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20)) and upper (PC25 MIF50) airway responsiveness to histamine, lower and upper airway inflammation using induced sputum and nasal lavage, in II patients with eosinophilic bronchitis. The authors assessed changes in these measures and in cough reflex sensitivity to capsaicin and cough severity after 400 microg of inhaled budesonide for 4 weeks. A nasal eosinophilia was present in only three patients with one having upper airway hyperresponsiveness. Following treatment with inhaled corticosteroids the geometric mean sputum eosinophil count decreased from 12.8% to 2.9% (mean difference 4.4-fold, 95% confidence interval (CI) 2.14-10.02), the mean +/- sem cough visual analogue score on a 100 mm scale decreased from 27.2 +/- 6.6 mm to 12.6 +/- 5.7 mm (mean difference 14.6, 95% CI 9.1-20.1) and the cough sensitivity assessed as the capsaicin concentration required to cause two coughs (C2) and five coughs (C5) improved (C2 mean difference 0.75 doubling concentrations, 95% CI 0.36-1.1; C5 mean difference 1.3 doubling concentration, 95% CI 0.6-2.1). There was a significant positive correlation between the fold change in sputum eosinophil count and doubling dose change in C5 after inhaled budesonide (r=0.61). It is concluded that upper airway inflammation is not prominent in eosinophilic bronchitis and that inhaled budesonide improves the sputum eosinophilia, cough severity and sensitivity suggesting a causal link between the inflammation and cough.

Administration, Inhalation↗

Asthma guidelines.

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Anti-Asthmatic Agents↗

TB guidelines.

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Antitubercular Agents↗

Sputum cysteinyl leukotrienes increase 24 hours after allergen inhalation in atopic asthmatics.

We have used the relatively noninvasive technique of induced sputum to measure allergen-induced changes in the concentration of eicosanoid mediators in bronchial secretions from atopic asthmatics. Sputum induction was performed before and 24 h after inhalational allergen challenge in 14 atopic asthmatics who developed a late asthmatic reaction (LAR). Differential cell counts were made on sputum cytospins and eicosanoid (cysteinyl leukotrienes [cys LTs], prostaglandin D(2) [PGD(2)], and PGE(2)) concentrations were measured in the sputum supernatants. The percentage of eosinophils at baseline correlated with the concentration of cys LTs (r = 0.84, p < 0.001) but not prostanoid mediators. Allergen challenge produced a significant increase in the concentration of sputum cys LTs from 3. 45 ng/ml sputum to 11.95 ng/ml (p = 0.002), which correlated with the increase in sputum eosinophils (r = 0.55, p < 0.05). There were no significant changes in PGD(2) or PGE(2) concentrations in sputum supernatants in response to challenge. Thus, the noninvasive technique of induced sputum has been used to demonstrate increased cys LTs, but not prostanoids associated with LAR after allergen challenge. The correlation between eosinophil numbers and cys LT concentrations at baseline values and 24 h after allergen challenge is consistent with these cells being a principal source of cys LTs within the airways at these time points.

Adult↗

Induced sputum inflammatory mediator concentrations in eosinophilic bronchitis and asthma.

Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but in contrast to asthma there is no variable airflow obstruction or airway hyperresponsiveness. Our hypothesis was that the differences in airway pathophysiology maybe due to less active airway inflammation in eosinophilic bronchitis, with reduced release of important effector mediators. We measured the concentration of various proinflammatory mediators in induced sputum cell-free supernatant in eight patients with eosinophilic bronchitis, 17 patients with asthma matched for sputum eosinophil count, and 10 normal subjects. Cysteinyl-leukotrienes (cys-LT) were measured by enzyme immunoassay, eosinophilic cationic protein (ECP) by fluoroimmunoassay, prostanoids (PGE(2), PGD(2), TXB(2), and PGF(2alpha)) by gas chromatography-negative ion chemical ionization-mass spectroscopy, and histamine by radioenzymic assay. The geometric mean sputum eosinophil count was similar in asthma (13.4%) and eosinophilic bronchitis (12.5%). Sputum cys-LT and ECP were a mean (95% CI) 1.6-fold (1.1, 2.5) and 6.4-fold (1.4, 28) higher in eosinophilic bronchitis and 1.9-fold (1.3, 2.9) and 7.7-fold (1.2, 46) higher in asthma compared with that in control subjects (geometric mean, 5.9 and 95 ng/ml, respectively). In eosinophilic bronchitis the mean concentration of sputum PGD(2) (0.79 ng/ml) and histamine (168 ng/ml) were significantly higher than in asthma (mean absolute difference in PGD(2) concentration, 0.47 ng/ml [95% CI, 0.19 to 0. 74] and mean-fold difference in histamine concentration, 6.7 [95% CI 1.7 to 26]) and normal subjects (0.64 ng/ml [0.36 to 0.90] and 11-fold [3.3 to 36]), respectively. In conclusion, eosinophilic bronchitis is associated with active airway inflammation with increased release of vasoactive and bronchoconstrictor mediators.

Adult↗

Eosinophilic bronchitis: an important cause of prolonged cough.

The recent development of noninvasive techniques to measure airway inflammation has led to the recognition of eosinophilic bronchitis, a condition characterized by a sputum eosinophilia identical to that seen in asthma, but without any of the functional abnormalities associated with asthma. The condition is interesting for a number of reasons. Firstly, eosinophilic bronchitis is a common cause of chronic cough, which is important to recognize as it responds well to corticosteroids. However, recognition is not straightforward because it requires assessment of airway inflammation. Secondly, the natural history of eosinophilic bronchitis is uncertain. Some patients with chronic obstructive pulmonary disease without a history of previous asthma have sputum eosinophilia, thus one possibility is that eosinophilic bronchitis may develop into fixed airflow obstruction. Finally, the difference in the association of eosinophilic airway inflammation to airway dysfunction between eosinophilic bronchitis and asthma is of interest as it is possible that it reflects important differences in the nature or site of the airway inflammation. Further study of this interesting condition may shed light on the relationship between airway inflammation and airway responsiveness, leading to a greater understanding of both eosinophilic bronchitis and asthma.

Algorithms↗

The safety and success rate of sputum induction using a low output ultrasonic nebuliser.

Induced sputum differential cell counts have been advocated as a method of non-invasively assessing airway inflammation in asthma and other airway diseases. Since sputum induction usually involves delivering hypertonic saline via a high output ultrasonic nebulizer there have been concerns about its safety in asthma. There are relatively little data on the effects of sputum induction in large numbers of patients. We have examined the success rate and effect of sputum induction on forced expiratory volume in 1 sec (FEV1) in 100 inductions performed on 79 patients using a low output nebulizer. Thirty-seven patients had asthma, 29 had miscellaneous conditions (mainly chronic cough) and 13 were subjects without respiratory symptoms. Sputum was induced 10 min after 200 micrograms of inhaled salbutamol by sequential 5-min inhalations of 3, 4 and 5% saline delivered via a Fisoneb ultrasonic nebulizer and FEV1 was measured after each inhalation. Sputum induction resulted in a sample suitable for analysis in 92% of asthmatics, 90% of those with miscellaneous conditions and 100% of normal subjects. The mean (SEM) maximum per cent fall in FEV1 was 5.4% (0.1), 4.3%, (1.0) and 2.6% (1.1) in subjects with asthma, miscellaneous conditions and in asymptomatic subjects respectively. Only 13 inductions resulted in a > 10% fall in FEV1, and only three of these resulted in a > 20% fall. The maximum per cent fall in FEV1 did not correlate with baseline FEV1 % predicted (r = -0.17), the log sputum eosinophil count (r = -0.12), or the methacholine PC20 (r = -0.14). We conclude that sputum induction using a relatively low output ultrasonic nebulizer with premedication with salbutamol is successful and safe in the majority of patients with asthma and other airway conditions.

Adolescent↗

Between-observer repeatability of sputum differential cell counts. Influence of cell viability and squamous cell contamination.

BACKGROUND: Induced sputum differential cell counts have been advocated as a method of noninvasively assessing airway inflammation in asthma and other airway diseases. Relatively little is known about the between-observer repeatability of sputum differential cell counts and the factors that influence it. OBJECTIVE: To assess the between-observer variability of induced sputum cell counts. METHODS: Sputum was induced and processed using standard techniques. Forty-two slides from 38 patients (31 with asthma, seven normal subjects) were randomly selected. Slides were classified as good (<20% squamous cells and >50% viability; n = 24); low viability (<50% viability; n = 10) and high squamous cell contamination (>20% squamous cells; n = 8). Two blinded observers counted between 200 and 400 nonsquamous cells and agreement was assessed by the intraclass correlation coefficient (ICC) and the standard deviation of between-observer differences (SD). RESULTS: The overall ICC were 0.9, 0.89, 0.9 for eosinophils, neutrophils and macrophages and 0.29 and 0.69 for lymphocytes and epithelial cells. Repeatability was greater in slides classified as good compared with slides with low cell viability and particularly excess squamous cell contamination. CONCLUSIONS: We have shown that the overall between-observer repeatability of the differential eosinophil, neutrophil and macrophage cell counts is good. Low cell viability and particularly excess squamous cell contamination reduce between-observer repeatability suggesting that techniques that ensure high cell viability and reduce squamous contamination would be an advantage.

Asthma↗