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Biomedical subjects

T Higenbottam

Publications and source records attributed to T Higenbottam.

At least 55 records · Page 3Linked to original sources
PubMed1994

The effect of anticholinergic bronchodilator therapy on cough during upper respiratory tract infections.

1. Oxitropium bromide (Oxivent), an anticholinergic bronchodilator, inhibits coughing induced by hypotonic aerosols in both asthmatic and non-asthmatic individuals. We have now extended this work to investigate whether this antitussive activity is reproducible in cough associated with viral infection. 2. The effect of oxitropium bromide (200 micrograms three times daily) on cough and pulmonary function has been studied in 56 non-asthmatic volunteers with upper respiratory tract infections (URTI) in a double-blind, randomised, parallel group, placebo controlled study over 10 days. 3. Lung function, symptom questionnaire and cough response to ultrasonically nebulised distilled water (UNDW) inhalation were initially recorded within 72 h of development of cough and again after the 10 day treatment period. By use of a diary card at home, frequency and severity of cough, nocturnal symptoms and general malaise were assessed daily throughout the treatment period using 5 cm visual analogue scales (VAS). Peak expiratory flow rate (PEFR) was recorded thrice daily before treatment over this 10 day period. 4. VAS scores of symptoms and UNDW-induced cough frequency all decreased over the 10 days of observation whether oxitropium bromide or placebo was administered. The mean PEFR showed a statistically significant fall in morning values during the early stages of infection which lessened with recovery but no effect of treatment with oxitropium bromide was observed (P > 0.05). 5. Oxitropium bromide, which inhibits the cough response to UNDW, does not offer an effective therapy for cough associated with an upper respiratory tract viral infection.

Adolescent↗
PubMed1994

Mixed expired nitric oxide in primary pulmonary hypertension in relation to lung diffusion capacity.

The mixed expired nitric oxide (NO) production of the lungs of patients with primary pulmonary hypertension (PPH) and normal subjects was measured to determine the relationship between NO production and the diffusion capacity of the lung (KCO). Expired air was collected from eight patients with PPH and 20 healthy volunteers for analysis by a chemiluminescent analyser. Mean pulmonary artery pressure in the PPH patients was 59.5 +/- 6.45 mmHg and their mean cardiac output was 2.95 +/- 0.35 l/min. All patients and subjects underwent measurements of FEV1, VC and KCO. The rate of production of NO in mixed exhaled air was lower in the PPH group compared to the controls (2.85 +/- 0.7 vs. 4.69 +/- 0.35 nM/min; p < 0.05). There was a good correlation of expired NO with the KCO (r = 0.7; n = 30; p < 0.001). When corrected, KCO differences in exhaled NO were not significant (p = 0.09). We conclude that the low exhaled NO observed in PPH patients is a reflection of the reduced blood capillary volume in these patients rather than a decreased basal production of NO.

Adult↗
PubMed1993

Measurement of exhaled nitric oxide in man.

BACKGROUND: Nitric oxide is released from pulmonary endothelial cells and contributes to the low pulmonary vascular resistance. The resistance pulmonary arteries are in close anatomical proximity to membranous airways, so it is likely that some pulmonary endothelial nitric oxide will enter the airspace to allow its measurement in the exhaled breath. METHODS: Exhaled air was collected from a single full exhalation and during tidal breathing. This was analysed for concentrations of nitric oxide, nitrogen dioxide, and carbon dioxide to give alveolar (FA) and mixed expired (FE) concentrations. Eight normal subjects were studied and laboratory air was similarly analysed using, respectively, chemiluminescent and infrared analysers. RESULTS: There was no relation between FA concentrations and the laboratory air concentrations. From the single breath, the ratio of (Fano/Faco2) x (Feco2/Feno) had a mean value of 0.92 (95% confidence interval 0.7 to 1.14). As this does not differ from unity, nitric oxide is likely to be derived from the same regions of the lungs as carbon dioxide. During tidal breathing the Feno ranged from 8.3 to 20.3 parts per billion. CONCLUSIONS: It is possible to measure endogenous pulmonary nitric oxide production in the exhaled air in man.

Adult↗
PubMed1993

Bronchoalveolar lavage and transbronchial lung biopsy during acute rejection and infection in heart-lung transplant patients. Studies of cell counts, lymphocyte phenotypes, and expression of HLA-DR and interleukin-2 receptor.

The total and differential cell counts of 135 bronchoalveolar lavages (BAL) in 48 heart-lung transplant (HLT) patients were compared with the histologic findings in concurrent transbronchial lung biopsies (TBBs). Counts of CD3+, CD4+, and CD8+ lymphocytes were recorded, and a semiquantitative assessment of HLA-DR and interleukin-2 receptor (IL-2R) expression was made on 29 occasions. There were five diagnostic categories: normal (n = 8), acute rejection (ALR) (n = 57), treated rejection (TR) (n = 19), infection (INF) (n = 24), and chronic rejection (CR) (n = 24). Total cell counts in INF were significantly higher than counts in all the other diagnostic groups. The highest BAL lymphocyte counts, significantly higher than in INF, were found in ALR because of increased CD8+ cells, exceeding 15% in 13 of 57 BALs. TBBs in ALR by contrast showed significantly increased numbers of both CD8+ and CD4+ cells. High dose corticosteroid treatment of ALR caused a fall in cellularity of BAL and TBB specimens but not always to values seen when patients were well. During INF and CR, significantly increased numbers of PMNs were seen in the BAL. HLA-DR and IL-2R expression was enhanced in cells of BAL and TBB in all complications. BAL can only supplement at present histologic examination of TBB in the diagnosis of complications after HLT.

Acute Disease↗
PubMed1993

Acute and chronic hypoxic pulmonary hypertension.

The development of secondary pulmonary hypertension (PH) as a result of pulmonary disease, both in adults and children, considerably worsens prognosis. Chronic hypoxia appears to be the cause, as long-term oxygen therapy (LTOT) reverses or at least impedes the progressive development of PH. There is now clear evidence that acute hypoxia causes smooth muscle contraction in pulmonary arteries through a direct effect on intracellular calcium levels. Subsequent relaxation depends upon activation of ion transport mechanisms which can be modified by circulating hormones such as the naturally occurring ouabain. Sustained hypoxia can cause adaptation of pulmonary endothelium. One change is a reduction in nitric oxide (NO) production, possibly through reduced activity of the formative enzyme nitric oxide synthase. Basal production of NO appears important in many species including man in determining the low pulmonary vascular resistance. Impaired endothelial NO production as a result of sustained hypoxia may well enhance the development of secondary PH. Much attention is now focused on the regulation of nitric oxide synthase, both the constitutive form in endothelium as well as the inducible form of inflammatory cells. It is possible that either gene transcription or translation are modified when endothelial cells are exposed to chronic hypoxia. This allows the opportunity for therapeutic intervention. More needs to be learnt about the cellular and molecular adaptation to hypoxia in man but novel approaches to treatment may soon arrive for patients with chronic obstructive lung disease and secondary pulmonary hypertension.

Amino Acid Oxidoreductases↗
PubMed1992

Evaluation of the International Society for Heart Transplantation (ISHT) grading of pulmonary rejection in 100 consecutive biopsies.

Heart-lung and lung transplantation are accepted treatments for patients with end-stage pulmonary vascular disease or parenchymal lung disease. Survival rates for heart-lung and lung transplantation are lower than those for heart transplantation alone. The 5-year actuarial survival for heart-lung transplantation has been 41% largely due to rejection and infection remaining as the limiting factors for long-term survival. A standardized nomenclature for the histological grading of pulmonary rejection was formulated by the International Society for Heart Transplantation (ISHT) in July 1990. Infection, however, is a major problem in the histological assessment of lung recipient biopsies, potentially limiting the usefulness of such a classification. In this study, 100 consecutive transbronchial biopsies (TBBs) from lung transplant recipients were analysed, together with microbiological and serological data, in order to evaluate the proposed ISHT grading system for pulmonary rejection and the importance of concomitant infections in the histological interpretation of TBBs.

Adolescent↗
PubMed1992

High dose nebulized steroid in the treatment of chronic steroid-dependent asthma.

Despite the dramatic success of inhaled steroids in controlling asthma symptoms there remains a small number of patients in whom asthma can only be treated with continuous oral steroids. Eighteen such patients, aged 19-62 years (seven males, 11 females) were followed in an open trial of nebulized budesonide over 12-18 months. All had required at least 7.5 mg or more daily prednisolone to control their symptoms over the preceeding 2 or more years and were taking 1200 micrograms beclomethasone dipropionate or 1600 micrograms budesonide daily. With a daily dose ranging between 4 and 8 mg nebulized budesonide, 14 patients successfully stopped oral steroids while in three the dose was reduced; only one patient failed to benefit. There was an increase in the mean FEV1 from 1.9 (+/- 0.9) to 2.2 (+/- 0.9) l, and in the mean morning PEFR, from 238 (+/- 119) to 286 (+/- 130) l min-1. There was also a significant decrease in the mean number of hospital admissions for acute severe asthma, from 1.5 (+/- 1.8) to 0.9 (+/- 1.1) per year. These findings should encourage a careful and controlled evaluation of nebulized steroids as a substitute for oral steroids in this difficult group of asthmatics.

Adult↗
PubMed1992

Late pulmonary haemodynamic changes in heart-lung transplantation.

As survival improves following heart-lung transplantation (HLT) the importance of obliterative bronchiolitis (OB) as a cause of late death increases. Whilst coronary occlusive disease (COD) may be less common in heart-lung transplant recipients than in patients receiving heart transplants, COD associated with OB can be lethal. We have studied 22 long-term survivors of heart-lung transplantation at an average of 25 months following transplantation during rest and at 50 W supine exercise and with prostacyclin induced vasodilation. Cardiac index increased less with exercise as the physiological measurement of OB using forced expiratory volume in one second (FEV1) fell (P = 0.018). Although resting pulmonary vascular resistance increased with falling FEV1, this increase was still within the normal range. We conclude that a fall in cardiac reserve on exercise accompanies the fall in FEV1 which characterizes OB and may reflect cardiac vascular disease.

Adult↗
PubMed1991

Pulmonary reflexes after human heart-lung transplantation.

Heart-lung transplantation involves denervation of the lungs below the tracheal anastomosis, with associated permanent loss of all pulmonary innervation except post-ganglionic efferent nerves. This is supported by loss of the cough reflex to inhaled USNDW, which also implies that the RARs which mediate this cough mechanism lie in the central airways. Bronchoconstriction following inhalation of USNDW developed only in those HLT recipients with acute lung rejection; this was not related to methacholine responsiveness and may therefore represent a pathologic vascular response. Hyperresponsiveness to methacholine has been reported following HLT, which we found unrelated to inflammation or acute rejection. A similar hyperresponsiveness to histamine was seen, which correlated with the response to methacholine. This also implies that histamine may act directly on smooth muscle receptors, and not solely via a cholinergic reflex. Hyperresponsiveness following HLT may be due to development of a generalized denervation hypersensitivity. Bronchodilation following capsaicin inhalation has been observed in HLT recipients, and may be due to unopposed release of VIP from retained post-ganglionic efferent nerves.

Aerosols↗