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Biomedical subjects

A T Hill

Publications and source records attributed to A T Hill.

12 recordsLinked to original sources
PubMed2001

Assessment of airway neutrophils by sputum colour: correlation with airways inflammation.

BACKGROUND: Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases. METHODS: To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum. RESULTS: The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001). CONCLUSIONS: These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.

Biomarkers↗
PubMed2000

Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis.

PURPOSE: Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation. SUBJECTS AND METHODS: We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation. RESULTS: Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function. CONCLUSIONS: The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.

Aged↗
PubMed2000

Airways inflammation in chronic bronchitis: the effects of smoking and alpha1-antitrypsin deficiency.

Airways inflammation in chronic bronchitis is thought predominantly to be a direct consequence of neutrophil recruitment and release of elastase in response to factors such as cigarette smoke. The aims of this study were to assess the role of smoking and determine whether the serum elastase inhibitor alpha1-antitrypsin (alpha1AT) influenced the process. Airways inflammation was compared between patients with chronic obstructive bronchitis with (n=39) and without (n=42) severe alpha1AT deficiency. The authors assessed the sputum concentration of the neutrophil chemoattractants interleukin-8 (IL-8) and leukotriene (LT)B4, myeloperoxidase (MPO) as a marker of neutrophil influx, neutrophil elastase activity and its natural inhibitors, alpha1AT and secretory leukoprotease inhibitor (SLPI). Finally serum alpha1AT was measured to determine the degree of protein leakage (sputum sol serum alpha1AT ratio). Compared to current smokers, the exsmokers had a lower concentration of the chemoattractant IL-8 (p<0.05) and a lower MPO concentration, although this failed to reach conventional statistical significance (p=0.06). Patients with alpha1AT deficiency had greater inflammation in the larger airways with increased LTB4 (p<0.005), MPO (p<0.001), neutrophil elastase activity (p<0.01), protein leak (p<0.001), and were found to have a lower anti-proteinase screen with both reduced sputum alpha1AT (p<0.001) and SLPI concentrations (p<0.05). The reduction in sputum interleukin-8 levels in exsmokers may decrease neutrophil influx and thus explain the slower rate of neutrophil mediated progression of lung disease compared to subjects who continue to smoke. Patients with alpha1-antitrypsin deficiency had greater inflammation suggesting that alpha1-antitrypsin plays an important role in protecting the larger airways from the inflammatory effects of elastase activity and may explain their more rapid progression of disease.

Adult↗
PubMed2000

Bronchial inflammation: its relationship to colonizing microbial load and alpha(1)-antitrypsin deficiency.

Neutrophil elastase is capable of generating many of the features of chronic bronchial disease. In patients with COPD, airways inflammation with neutrophil recruitment and elastase release is positively correlated with colonizing bacterial load in the stable clinical state (p < 0.0005). In addition, alpha(1)-antitrypsin deficiency is associated with a greater neutrophil load, higher elastase activity, leukotriene-B(4) concentration, and serum protein leak than matched patients without deficiency (p < 0.005). These data confirm an effect of bronchial colonization on airways inflammation in COPD and indicate the role of alpha(1)-antitrypsin in its modulation.

Bacteria↗
PubMed1999

Chronic obstructive pulmonary disease, with and without alpha-1-antitrypsin deficiency: management practices in the U.K.

Alpha-1-antitrypsin deficiency is a common genetic defect associated with the development of severe and rapidly progressive lung disease. This study was undertaken to determine whether respiratory physicians manage patients with alpha-1-antitrypsin (AAT) deficiency differently from patients with chronic obstructive pulmonary disease (COPD) without alpha-1-antitrypsin deficiency. In addition we obtained physicians' views on who should be tested for AAT deficiency. A questionnaire was administered to 88 respiratory physicians based throughout the U.K. (44 in teaching hospitals). The main outcome measures were pulmonary function tests, radiological assessment, frequency of repeat testing, follow-up and screening protocol for alpha-1-antitrypsin deficiency. Subjects with homozygous (PiZ) AAT deficiency were more likely to: 1. have baseline and full pulmonary function testing including dynamic flow rates, static lung volumes, and gas transfer; 2. have more comprehensive assessment with high resolution computed tomography (HRCT) thorax and repeated radiological assessment (with annual chest radiography); 3. be followed-up routinely; and 4. have family members tested for alpha-1-antitrypsin deficiency. Testing remains limited for AAT deficiency and is mainly restricted to young patients with COPD. COPD assessment and management is influenced by the presence of AAT deficiency, which may reflect the poorer prognosis of such patients due to more rapid decline. Assessment and monitoring could be simplified to forced expired manoeuvres, although limited HRCT thorax and tests of gas transfer may prove more sensitive to progression of emphysema. Testing for AAT deficiency in the U.K. remains restricted, which will influence the detection rate for AAT deficiency. A wider policy of testing was advocated by the WHO will detect more patients and also influence our understanding of the natural history of the condition.

Adult↗
PubMed1999

The interrelationship of sputum inflammatory markers in patients with chronic bronchitis.

Many of the features of bronchial disease are believed to be caused by damage to the airways by elastase released by recruited neutrophils. There have been few studies of the mechanisms involved and the interrelationships between components of the inflammatory process. We studied secretions from patients with chronic bronchitis in the stable state. We assessed the presence of neutrophils by measuring myeloperoxidase (MPO) activity and active neutrophil elastase (NE). These results were compared with the chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)), the bronchial inhibitor secretory leukoprotease inhibitor (SLPI), and protein leak (sputum/serum albumin ratio). MPO correlated with NE activity (r = 0.68, p < 0.001) and both IL-8 (r = 0.52, p < 0.001) and LTB(4) (r = 0.41, p < 0.001) indicating an association with the chemoattractants. Elastase activity correlated with IL-8 (r = 0.55, p < 0.001) and LTB(4) (r = 0.41, p < 0.001) but negatively with SLPI (r = -0.49, p < 0.001). NE also correlated positively with protein leak (r = 0.36, p < 0.001), suggesting a cause and effect. MPO and protein leak correlated negatively with FEV(1) (percentage of predicted) only in patients with chronic obstructive pulmonary disease (COPD) without alpha(1)-antitrypsin deficiency (r = -0.37, p < 0.001; r = -0.42, p < 0.01, respectively). These complex interactions provide a template for future studies with specific inhibitors or agonists which will clarify the role of individual factors.

Adult↗
PubMed1999

Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (PiZ).

Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.

Acute Disease↗
PubMed1998

Ventilation in a Birmingham intensive care unit 1993-1995: outcome for patients with chronic obstructive pulmonary disease.

The aims of the study were to look at information on which the decision to ventilate chronic obstructive pulmonary disease (COPD) patients admitted to an intensive care unit (ITU) was based (including whether there was discussion with the patient, relatives and consultant), to identify indicators of poor prognosis, and to assess the outcomes of ventilation and functional capacity after discharge. A retrospective study of 27 months of admissions was carried out. The following variables were studied to see if they influenced prognosis: premorbid history, admission diagnosis, consultant involvement in the decision to transfer to ITU, admission chest radiograph, sputum bacteriology, arterial blood gases, APACHE II scores, duration of ventilation and complications in ITU. In-hospital mortality, post-discharge mortality and length of hospital stay were recorded. Functional capacity after discharge was assessed from the hospital clinic records and from general practitioners. Forty-six percent of case notes had inadequate premorbid information and no documented discussion occurred in 66% of patients/relatives. Poor prognostic indicators were admissions after cardiorespiratory arrest, cases discussed with consultants regarding ITU transfer, previous therapy with long-term oral steroids, and developing renal or cardiac failure in ITU. APACHE II scores were higher in the group that died. There was 49% hospital mortality and 59% 1-year mortality. Fifty-three percent of survivors were dependent upon carers and housebound, and general practitioners felt that 59% of survivors had a higher dependence on carers, a worse exercise tolerance and a poorer quality of life than before admission. The decision to ventilate is often made with inadequate background history, which could be sought from general practitioners, hospital case notes and family. There is significant morbidity and mortality following ventilation. Further prospective studies are required to help select which COPD patients should be ventilated.

APACHE↗
PubMed1998

Long-term nasal intermittent positive pressure ventilation in patients with cystic fibrosis and hypercapnic respiratory failure (1991-1996).

In patients with cystic fibrosis (CF), nasal intermittent positive pressure ventilation (NIPPV) is currently used as a short-term bridge to transplantation but its precise role has yet to be determined. Patients were offered a therapeutic trial of NIPPV when candidates for lung transplantation, with respiratory failure unresponsive to medical treatment. Twelve patients, six male of mean age of 26 +/- 1.4 years, had a trial of NIPPV. At recruitment the mean percentage predicted forced expired volume in one second (FEV1) was 15.1% +/- 1.2%, arterial carbon dioxide (PaCO2) 8.7 +/- 0.6 kPa, arterial oxygen (PaO2) with variable FiO2 7.4 +/- 0.6 kPa and arterial bicarbonate (HCO3-) 40.1 +/- 1.6 mmol l-1. Ten cases tolerated NIPPV for 1-15 months, mean 5.1 +/- 1.4 months, with subjective improvement in headache and quality of sleep. At 3 months, there was significant improvement in forced vital capacity, PaCO2 and arterial HCO3- and there was a reduction in the number of hospital inpatient days (P < 0.05). Subsequently three cases had lung transplantation, four died on the active list and three are awaiting organs. Two patients failed to tolerate NIPPV owing to abdominal bloating and increasing hypercapnia. In conclusion, NIPPV, if tolerated, was a useful adjunct in the treatment of CF patients with hypercapnic respiratory failure awaiting transplantation. Further prospective studies are required to determine the optimum time to commence NIPPV and to clarify its precise role.

Adult↗
PubMed1998

Percutaneous transseptal mitral valvotomy--progress report.

BACKGROUND: Percutaneous transseptal mitral valvotomy (PTMV) has been established as an alternative to surgery in the treatment of mitral stenosis. AIM: To review our experience in the first 200 attempted PTMV procedures in patients with mitral stenosis, and the short and medium term follow-up. METHODS: PTMV was attempted on 200 occasions in 189 patients with significant mitral stenosis between May 1988 and May 1994. There were 156 females and 33 males, mean age 53.5 years (range 14 to 83 years). Six patients were pregnant at the time of the procedure. RESULTS: Valve split was achieved at the initial attempt in 183/189 procedures (97%). Clinical improvement of at least one New York Heart Association (NYHA) functional class was achieved in 172/189 patients (91%). The mean mitral valve gradient (mean +/- SD) decreased from 11.5 +/- 5.1 mmHg to 4.9 +/- 4.1 mmHg, mean cardiac output rose from 3.9 +/- 1.1 L/minute to 4.4 +/- 1.4 L/minute and mean calculated mitral valve area increased from 1.0 +/- 0.3 cm2 to 2.1 +/- 0.9 cm2. Ten patients developed clinically significant mitral incompetence requiring surgical mitral valve replacement. There were two transient cerebral embolic events. Small atrial septal defects were detected echocardiographically in 42 patients, but none has been a clinical problem. There were no early deaths; there were 11 late deaths, four of which were non-cardiac. Twenty patients have had repeat PTMV for re-stenosis, four to 67 months after the first. CONCLUSIONS: PTMV provides significant haemodynamic and clinical improvement with low risk and should be considered the treatment of choice in patients with mitral stenosis.

Adolescent↗