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Biomedical subjects

P Howarth

Publications and source records attributed to P Howarth.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗
PubMed2005

Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma.

BACKGROUND: Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma. METHODS: A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts. RESULTS: Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness. CONCLUSIONS: In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.

Administration, Inhalation↗
PubMed2002

The association between diet and chronic obstructive pulmonary disease in subjects selected from general practice.

It is unclear why some smokers develop chronic obstructive pulmonary disease (COPD) whilst the majority do not. Antioxidants found in food may protect against lung tissue injury, but previous epidemiological studies are inconsistent and do not focus on those most at risk of COPD, namely smokers. This case-controlled study measured the difference in dietary intake between smokers and exsmokers with and without COPD. Cases were patients > 45 yrs of age with > 10 pack-yrs of smoking, a forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of < or = 70% and a FEV1 of < or = 80% of predicted. Controls were patients >45 yrs of age with > 10 pack-yrs of smoking, a FEV1/FVC of > 70% and a FEV1 > 80% pred. Data were collected using validated questionnaires. Logistic regression analysis for an unmatched case-controlled study was performed. After controlling for other independent predictors of COPD, those with vegetable intake of > or = 1 portion x day(-1) (93 g) were less likely to have COPD, as were those consuming > or = 1.5 portions x day(-1) of fruit. This was not due to an overall reduction in food/calorie intake caused by the disease because: 1) adjusting for body mass index did not alter the estimates; 2) the effect was specific to fruit and vegetables, i.e. not other food groups; and 3) the estimates from incident cases were similar. In conclusion, fruit and vegetable consumption is inversely associated with chronic obstructive pulmonary disease and may explain why some smokers do not develop chronic obstructive pulmonary disease.

Adult↗
PubMed2000

Transfer of telemedical support to Cornwall from a national telemedicine network during a solar eclipse.

During late 1998 and early 1999, planning officers in Cornwall predicted a huge increase in summer visitors to the county to observe the August solar eclipse. There was the possibility that a mass gathering in Cornwall could overload existing arrangements for handling accident and emergency patients. We therefore set up a telemedicine system to support the county's minor injury units (MIUs) from hospitals throughout the UK. Six main hospital accident and emergency departments outside Cornwall with existing links to their own MIUs were twinned with 10 of the 11 MIUs in Cornwall before the expected date of the gathering. The network was live for nine days, starting four days before the eclipse, and 2045 patients were seen in the 10 MIUs. There were 93 telemedicine calls from the 10 MIUs, involving 91 patients. Overall, 4.6% of the patients required a telemedicine consultation. Fifty-seven calls were made during working hours. Thirty-four patients were referred for further management, of whom 18 were referred on the same day. The transfer of telemedical support to a national network was successful.

Emergency Medical Services↗
PubMed2000

An exploratory study of information-giving used to promote chlamydial test-seeking by students at a college family planning clinic.

Partnership working, involving workers in various aspects of sexual health and a large UK further education college, took place to give information about genital tract chlamydial infection in order to promote chlamydial urine testing (LC(x) Chlamydia trachomatis Assay Abbott Diagnosis Division) for a limited period at the college's family planning clinic. Female students were more likely to report awareness about the availability of testing and to access the testing service. Uptake of testing was largely contemporaneous with information-giving work and sharply declined after information-giving had ceased. A small population of test seekers (including partners of index cases) was generated, which harvested a rate of genital tract chlamydial infection similar to that found in family planning and genitourinary medicine clinics.

Ambulatory Care Facilities↗
PubMed1999

Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma.

BACKGROUND: The matrix metalloproteinase (MMP) enzymes MMP-3 and MMP-9 have relevance to the chronic structural airway changes in asthma. These proteinases can be generated by structural and inflammatory cells, and have the ability to degrade proteoglycans and thus potentially enhance airway fibrosis and smooth muscle proliferation through their ability to release and activate latent matrix bound growth factors. METHODS: Immunostaining for MMP-3 and MMP-9 as well as for mast cells, eosinophils, and neutrophils was undertaken in acetone fixed and glycolmethacrylate embedded endobronchial biopsy specimens obtained by fibreoptic bronchoscopy under local anaesthesia. The findings from 17 asthmatic subjects (nine with mild to moderate non-steroid treated asthma and eight with chronic persistent steroid-dependent asthma) were compared with those from eight healthy controls. The cell associated MMP immunoreactivity was co-localised to mast cells, eosinophils, or neutrophils and represented as cells/mm2, based on the area of the biopsy specimen. Extracellular matrix immunoreactivity was assessed by an image analysis system and visually with ranking and the two approaches were compared. RESULTS: The biopsy specimens from asthmatic subjects contained significantly more eosinophils (p<0. 001) than those from the non-asthmatic subjects. Both MMP-9 and MMP-3 immunoreactivity could be identified in endobronchial biopsy specimens. Gelatinase B (MMP-9) immunoreactivity was prominent within the extracellular matrix as well as exhibiting distinct cell immunoreactivity which predominantly co-localised to neutrophils. Stromelysin (MMP-3) was co-localised to mast cells, eosinophils, and neutrophils as well as being present in the epithelium, the lamina reticularis and, to a lesser extent, the extracellular matrix. There was no significant difference in the extent of matrix immunoreactivity for either MMP-3 or MMP-9 between healthy controls or subjects with mild or severe asthma. CONCLUSION: Although immunostaining cannot distinguish between active and inactive forms of MMPs, the presence of MMP-3 and MMP-9 within endobronchial biopsy specimens, the co-localisation to inflammatory cells of relevance to asthma (mast cells and eosinophils), and the identification of matrix binding, indicative of MMP-matrix interactions, points to the potential for disease related changes in MMP release that influence airway remodelling in asthma.

Adult↗
PubMed1999

The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.

The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment

Administration, Inhalation↗
PubMed1998

Small airway inflammation and asthma.

Evidence derived from large airways has shown that asthma involves mucosal inflammation and structural airway changes including fibroblast proliferation and collagen deposition. Techniques, such as transbronchial biopsy and bronchoalveolar lavage as well as analysis of resected or post-mortem tissue, indicate that similar inflammatory and structural airway changes exist in the small airways in asthma. This paper reviews the evidence that inflammatory and structural changes occur throughout the airways in asthma and discusses the relevance of these considerations. In addition, analysis of resected lung tissue from asthmatic subjects has revealed increased numbers of activated eosinophils within the small airways, when compared with the large airways. Transbronchial biopsy studies in patients with nocturnal asthma have now also identified eosinophilic inflammation within the alveolar walls which correlates with the nocturnal physiological changes. The implications of these findings is that anti-inflammatory treatment needs to be directed to both the large and small airways to achieve the maximal suppression of inflammation throughout the airways.

Asthma↗
PubMed1998

The effect of acupuncture on nonallergic rhinitis: a controlled pilot study.

The purpose of this pilot project was to evaluate the immediate effects of real acupuncture compared with two placebo controls (sham acupuncture and mock transcutaneous electrical nerve stimulation) in the treatment of nonallergic rhinitis patients. These three treatments were given in a nonrandomized order to the same patients at weekly intervals. Real acupuncture showed an improvement in nasal airways resistance after treatment in 9 of 13 patients, sham acupuncture in 2 of 9, and mock transcutaneous electrical nerve stimulation in 3 of 10 patients. With the exception of improvement in a minimal cross-sectional area (measured by acoustic rhinometry) in the real acupuncture group following treatment, the outcome was not statistically significant. This pilot study raised a number of issues related to the effects of acupuncture in nonallergic rhinitis that must be addressed by a study involving more patients in which the order of treatment is randomized and the two placebo control treatments are evaluated in relation to their credibility.

Acupuncture Therapy↗
PubMed1997

The effect of treatment with oral corticosteroids on asthma symptoms and airway inflammation.

To improve understanding of the mechanisms of action of oral corticosteroids in asthma, we have conducted a double-blind, placebo-controlled study with prednisolone (20 mg for 2 wk followed by 10 mg for 4 wk) or placebo in 14 and 13 atopic corticosteroid-naive asthmatic subjects, respectively. Before and after treatment subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy. Treatment with prednisolone, but not placebo, significantly reduced asthma symptoms (from mean +/- SEM total weekly score of 34 +/- 6.2 to 15.7 +/- 3.2, p = 0.02) and albuterol usage (from mean +/- SEM number of puffs/wk of 29.7 +/- 6.2 to 18.2 +/- 3.7, p = 0.01) and significantly increased FEV1 (from 89.8 +/- 4.4% to 99.3 +/- 4.1% of predicted, p = 0.03). There were no significant changes in inflammatory or epithelial cell counts, levels of T-cell activation or albumin concentration in BAL. However, immunohistochemistry of bronchial biopsies showed that in the submucosa prednisolone significantly decreased numbers of mast cells by 62% (from median 45 to 17/mm2, p = 0.01), eosinophils by 81% (from median 30.1 to 5.7/mm2, p = 0.004), and CD4+ T-cells by 68% (from median 64.6 to 18.5/mm2, p = 0.02). In the epithelium only the reduction in the numbers of eosinophils was significant (from median 1.1 to 0/mm of epithelium, p = 0.02). There were no significant changes in any cell counts in the subjects receiving placebo, and comparison of the changes between the treatment groups identified a significant prednisolone-related reduction in submucosal eosinophil and mast cell counts (p = 0.003 and 0.03, respectively). The temporal association between the clinical and physiologic improvement, and the correlation between the magnitude of change in CD4+ T-cell counts in the submucosa and increase in PC20 methacholine (rs = 0.60, p = 0.049) suggests that the reduction in airways inflammatory cell numbers underlies the clinical efficacy of oral corticosteroids.

Administration, Oral↗
PubMed1996

Increased levels of exhaled nitric oxide during nasal and oral breathing in subjects with seasonal rhinitis.

BACKGROUND: Allergic rhinitis is associated with nasal mucosal inflammation. Exhaled nitric oxide may be a useful marker of inflammation and has recently been shown to be increased in patients with asthma. OBJECTIVE: The purpose of this study was to determine whether exhaled levels of nitric oxide are increased with nasal breathing in patients with seasonal allergic rhinitis compared with nonatopic individuals and whether there is an increase with oral breathing consistent with lower respiratory inflammation in the absence of clinical asthma. METHODS: Nitric oxide levels in exhaled air were measured by chemiluminescence in 18 nonatopic volunteers and 32 patients with seasonal rhinitis. Measurements were made with both nasal and oral exhalation and orally after 10 seconds and 60 seconds of breath-holding. The detection limit was 1 part per billion (ppb). RESULTS: In control subjects nasal levels of nitric oxide in exhaled air (mean +/- SD, 24.7 +/- 9.2 ppb) were higher than those after oral exhalation (11.1 +/- 2.5 ppb, p less than 0.0001). Breath-holding significantly increased levels of nitric oxide in exhaled air in a time-dependent manner. Levels of exhaled nitric oxide were significantly higher for all measurements in patients with seasonal rhinitis, with levels without breath-holding of 35.4 +/- 11.3 ppb (p less than 0.001) in nasally exhaled air and 16.3 +/- 5.9 ppb (p less than 0.001) in orally exhaled air. Nasal levels were significantly higher than oral levels in subjects with rhinitis (p less than 0.0001). CONCLUSIONS: The results indicate that exhaled nitric oxide may be a useful marker for nasal inflammation in patients with seasonal rhinitis and suggest that generalized airway inflammation may be present, even without clinical asthma, in such patients.

Adult↗
PubMed1993

Diary keeping in asthma: comparison of written and electronic methods.

OBJECTIVE: To determine the extent to which symptom diaries of asthmatic patients are inaccurate or based on retrospective recall. DESIGN: Comparison of electronic and pencil and paper diaries. Both forms were completed twice daily at home for 14 days. SETTING: Outpatient clinic. SUBJECTS: 24 asthmatic outpatients also tested for severity of asthma and for anxiety. RESULTS: More sessions were missed in the evening than in the morning for both types of diaries. Significantly more retrospective entries were made in the evening (26 entries, 14 patients) than in the morning (6 entries, 3 patients). Discrepant entries of peak expiratory flow accounted for 15% of those made on the appropriate day, and three quarters of patients made at least one discrepant entry. Variation in peak expiratory flow was significantly related to number of discrepancies and number of missing days, and anxiety score was significantly related to number of missing days. About a fifth of written entries may have errors. CONCLUSION: Poor diary completion may result from having unreasonable expectations of patients and giving incomplete instructions. Electronic, time coded diaries could ensure better quality of records.

Asthma↗
PubMed1993

Mechanisms of airways inflammation which may be amenable to prophylaxis.

The presence of mucosal inflammation in the lower airways of atopic asthmatics and to a milder degree of atopic nonasthmatics suffering from rhinitis points to atopy and allergen exposure as risk factors for lower airways disease. The study of mechanisms which regulate the degree of inflammation should enable the understanding of why some individuals suffer from rhinitis alone whereas others go on to develop bronchial disease. This information should enable the development of prophylactic strategies to prevent atopy from expressing itself in the lower airways.

Air Pollutants↗
PubMed1991

The need for a pathological classification of asthma.

Historically, asthma has been described in functional terms as reversible airways obstruction and bronchial hyperresponsiveness. Whilst there is no agreed definition of asthma, studies involving bronchoalveolar lavage and endobronchial biopsy are highlighting inflammatory processes as an essential component of the disorder. With the success already achieved in quantifying mast cells, neutrophils, eosinophils, T-cells, monocytes and fibroblasts in the bronchial mucosa it should be possible to investigate the cellular basis of asthma, both in relation to clinical patterns of disease and their response to treatment. With such information it may well be possible that a definition of asthma could be arrived at based on pathology rather than function alone.

Asthma↗