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Biomedical subjects

L G Heaney

Publications and source records attributed to L G Heaney.

32 records · Page 2Linked to original sources
PubMed1998

Neurokinin A is the predominant tachykinin in human bronchoalveolar lavage fluid in normal and asthmatic subjects.

BACKGROUND: Multiple sensory neuropeptides are present in human airways and may contribute to diseases such as asthma. This study quantified and characterised substance P (SP), neurokinin A (NKA), and calcitonin gene related peptide (CGRP) immunoreactivity in bronchoalveolar lavage fluid in asthmatic and normal subjects. METHODS: Using specific radioimmunoassay (RIA), SP, NKA and CGRP were measured in bronchoalveolar lavage fluid from asthmatic subjects (n = 5), normal subjects (n = 5), atopic non-asthmatic subjects (n = 6), and asthmatic subjects four hours after allergen challenge (n = 12). Peptide immunoreactivity was characterised using high performance liquid chromatography (HPLC) and RIA. RESULTS: No SP or CGRP immunoreactivity was detected in any of the fractions from samples after extraction, HPLC, and RIA. Non-specific binding resulted in spurious SP immunoreactivity being detected in bronchoalveolar lavage fluid when no extraction process was employed. NKA was detected in significant amounts in asthmatic (median 550, range 425-625 pg/ml) and normal subjects (median 725, range 350-1425 pg/ml). The level of NKA was significantly higher in the asthmatic subjects after allergen challenge (median 750, range 350-1250 pg/ml) than in unchallenged asthmatic subjects (median 600, range 425-600 pg/ml, p < 0.01). CONCLUSIONS: Extraction and characterisation of peptides from bronchoalveolar lavage fluid must be performed to ensure that the measured immunoreactivity represents target peptide. NKA is present in bronchoalveolar lavage fluid in high concentrations and is the predominant tachykinin. The concentrations of NKA are similar in normal subjects and subjects with mild asthma.

Adolescent↗
PubMed1998

Evaluation and outcome of patients with chronic non-productive cough using a comprehensive diagnostic protocol.

BACKGROUND: Asthma, post-nasal drip syndrome (PNDS), and gastro-oesophageal reflux (GOR) account for many cases of chronic non-productive cough (CNPC). Each may simultaneously contribute to cough even when clinically silent, and failure to recognise their contribution may lead to unsuccessful treatment. METHODS: Patients (all lifetime non-smokers with normal chest radiographs and spirometric measurements) referred with CNPC persisting for more than three weeks as their sole respiratory symptom underwent histamine challenge, home peak flow measurements, ear, nose and throat (ENT) examination, sinus CT scanning, and 24 hour oesophageal pH monitoring. Treatment was prescribed on the basis of diagnoses informed by investigation results. RESULTS: Forty three patients (29 women) of mean age 47.5 years (range 18-77) and mean cough duration 67 months (range 2-240) were evaluated. On the basis of a successful response to treatment, a cause for the cough was identified in 35 patients (82%) as follows: cough variant asthma (CVA) (10 cases), PNDS (9 cases), GOR (8 cases), and dual aetiologies (8 cases). Histamine challenge correctly predicted CVA in 15 of 17 (88%) positive tests. ENT examination and sinus CT scans each had low positive predictive values for PNDS (10 of 16 (63%) and 12 of 18 (67%) positive cases, respectively), suggesting that upper airways disease frequently co-exists but does not always contribute to cough. When negative, histamine challenge and 24 hour oesophageal pH monitoring effectively ruled out CVA and GOR, respectively, as a cause for cough. CONCLUSION: This comprehensive approach aids the accurate direction of treatment and, while CVA, PNDS and GOR remain the most important causes of CNPC to consider, a group with no identifiable aetiology remains.

Adolescent↗
PubMed1997

Histamine release from human bronchoalveolar lavage mast cells by neurokinin A and bradykinin.

OBJECTIVE AND DESIGN: This study examined whether bradykinin and neurokinin A activate human pulmonary mast cells retrieved by bronchoalveolar lavage (BAL). SUBJECTS: BAL samples were obtained at routine bronchoscopy from 14 unpreselected patients. METHODS: Histamine release experiments were performed using substance P, neurokinin A, bradykinin (peptides 25 and 50 microM), compound 48/80 (0.75-10 micrograms/ml) and A23187 (1 microM). Statistical analyses were performed using the paired Student's t-test and Pearson's linear correlation coefficient. RESULTS: Compound 48/80 induced release was significantly lower than that induced by the other secretagogues (p < 0.05). Neurokinin A and bradykinin induced release correlated significantly with substance P induced release (p < 0.01), suggesting similar mechanisms of action. No correlations were observed between neurokinin A or bradykinin-induced release and the non-peptide stimuli studied. CONCLUSIONS: The mechanism of neurokinin A- and bradykinin-induced bronchoconstriction is not yet clear but our data suggest an indirect effect mediated by mast cell degranulation.

Bradykinin↗
PubMed1997

Brewer's asthma due to malt contamination.

We describe a case of a 28 year old brewery worker who developed asthma whilst grinding malt. Lung function measurements demonstrated deterioration and improvement in lung function associated with work and absence from work. Inhalation challenge with ground malt from the brewery was positive but with ground malt from another source was negative suggesting a contaminant of the malt was responsible. Culture of the brewery malt showed heavy contamination with Aspergillus niger, but A. niger skin test was negative and aspergillus-specific IgG was not detected in the patients serum. Removal of the subject from the grinding room resulted in resolution of symptoms and normal lung function. We discuss the role of A. niger as an aetiological agent for occupational asthma with reference to the above case.

Adult↗
PubMed1997

Bronchoalveolar lavage findings suggest two different forms of childhood asthma.

BACKGROUND: It seems plausible that children with atopy and persistent asthma symptoms will, like their adult counterparts, have chronic airways inflammation. However, many young children with no other atopic features have episodic wheezing that is triggered solely by viral respiratory infections. Little is known as to whether airways inflammation occurs in these two asthma patterns during relatively asymptomatic periods. METHODS: Using a non-bronchoscopic bronchoalveolar lavage (BAL) procedure on children presenting for an elective surgical procedure, this study has investigated the cellular constituents of BAL fluid in children with a history of atopic asthma (AA) non-asthmatic atopic children (NAA) or viral associated wheeze (VAW). RESULTS: A total of 95 children was studied: 52 with atopic asthma (8.0 years, range 1.1-15.3, 36 male), 23 with non-asthmatic atopy (median age 8.3 years, range 1.7-13.6, 11 male) and 20 with VAW (3.1 years, range 1.0-8.2, 13 male). No complications were observed during the lavage procedure and no adverse events were noted post-operatively. Total lavage fluid recovered was similar in all groups and the total cell numbers were higher in the VAW group. Eosinophil (P < or = 0.005) and mast cell (P < or = 0.05) numbers were significantly elevated in the group with atopic asthma. CONCLUSIONS: During relatively asymptomatic periods there is on-going airways inflammation, as demonstrated by eosinophil and mast cell recruitment, in children with asthma and atopy but not in children with viral associated wheeze or atopy alone. This strongly suggests that there are different underlying pathophysiological mechanisms in these two groups of children who wheeze.

Adolescent↗
PubMed1997

A comparison of three standard methods of identifying mast cells in endobronchial biopsies in normal and asthmatic subjects.

Reported mast-cell counts in endobronchial biopsies from asthmatic subjects are conflicting, with different methodologies often being used. This study compared three standard methods of counting mast cells in endobronchial biopsies from asthmatic and normal subjects. Endobronchial biopsies were obtained from atopic asthmatic subjects (n = 17), atopic nonasthmatic subjects (n = 6), and nonatopic nonasthmatic control subjects (n = 5). After overnight fixation in Carnoy's fixative, mast cells were stained by the short and long toluidine blue methods and antitryptase immunohistochemistry and were counted by light microscopy. Method comparison was made according to Bland & Altman. The limits of agreement were unacceptable for each of the comparisons, suggesting that the methods are not interchangeable. Coefficients of repeatability were excellent, and not different for the individual techniques. These results suggest that some of the reported differences in mast-cell numbers in endobronchial biopsies in asthma may be due to the staining method used, making direct comparisons between studies invalid. Agreement on a standard method is required for counting mast cells in bronchial biopsies, and we recommend the immunohistochemical method, since fixation is less critical and the resultant tissue sections facilitate clear, accurate, and rapid counts.

Adolescent↗
PubMed1997

Prescription of oxygen concentrators and survival in Northern Ireland.

Long-term oxygen therapy (LTOT) has been shown to prolong survival and to improve quality of life in patients with chronic obstructive pulmonary disease (COPD) and in respiratory failure. In Northern Ireland oxygen concentrators have been available on prescription since August 1986, initially on a restricted basis from hospital physicians only. This was followed by open prescribing from April 1989, when concentrators could be prescribed by general practitioners. This study examined prescribing habits of LTOT during both periods, and patient survival. Case notes of all prescriptions of oxygen concentrators in Northern Ireland (to April 1991) were reviewed. Prescription criteria and advice regarding usage during both periods were analysed. A questionnaire survey of subjects during open prescribing documented the advice given at the time of prescription and current usage. 164 charts of 178 total installations were available for review. During both periods many concentrators were installed without adherence to the prescribing criteria at the time (75% restricted, 48% open). The majority of these were on the advice of a consultant respiratory physician and only 14 were prescribed directly by GPs. 89 of 91 subjects receiving current LTOT during the study period completed questionnaires. Of the subjects prescribed LTOT during the restricted period, 2 subjects are still alive (median survival 19 m, range 0-104). From the open period, survival data was available on 107 of 129 subjects with 17 still alive (median survival 22 m, range 0-94). This study documents an inadequate rate of prescribing and a lack of conformity to guidelines in the provision of LTOT in Northern Ireland. We would suggest that familiarisation with the prescribing criteria, formal written advice at the time of prescription, appropriate follow up to ensure adequate supplementation and regular patient education on the use of LTOT would address these problems to a substantial degree.

Aged↗
PubMed1996

Investigating paediatric airways by non-bronchoscopic lavage: normal cellular data.

BACKGROUND: Bronchoscopic bronchoalveolar lavage in children to investigate bronchial disorders such as asthma has both ethical and procedural difficulties. OBJECTIVE: The aim of this study was to establish a standardized non-bronchoscopic method to perform bronchoalveolar lavage in children attending for elective surgery to obtain normal cellular data. METHODS: Bronchoalveolar lavage was performed on normal children (n = 55) by infusing saline (20 mL) through an 8 FG suction catheter passed after endotracheal intubation. Oxygen saturation, heart and respiratory rate were monitored during the bronchoalveolar lavage procedure. Cellular analysis and total protein estimation of the lavage fluid were performed. Epithelial lining fluid volume was calculated (n = 15) using the urea dilution method. RESULTS: The procedure was well tolerated by all children. Total cell count and differential cell count for children (macrophages 70.8 +/- 2.3%, lymphocytes 3.8 +/- 0.6%, neutrophils 5.7 +/- 1.0%, eosinophils 0.14 +/- 0.03%, epithelial cells 19.6 +/- 2.1%, mast cells 0.21 +/- 0.02%) were similar to those reported for adults. Age and sex comparisons revealed no differences between groups. The mean total protein recovered in the cell free supernatant was 49.72 +/- 4.29 mg/L and epithelial lining fluid volume was 0.82 +/- 0.11% of return lavageate. CONCLUSION: This method allows bronchoalveolar lavage to be performed safely and quickly on children attending for routine elective surgery. Using this method and taking the 'window of opportunity' of elective surgery, the presence or absence of airway inflammation could be studied in children with various patterns of asthma during relatively asymptomatic periods.

Adolescent↗
PubMed1995

Substance P induces histamine release from human pulmonary mast cells.

Substance P elicits histamine release from human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, we examined the ability of substance P to stimulate human mast cells obtained at bronchoalveolar lavage (BAL). BAL samples were obtained at routine bronchoscopy from 35 non-preselected patients. Histamine release experiments were performed in a standard manner using substance P and the calcium ionophore A23187. Both substance P (50 microM) and A23187 caused histamine release (median 26.7% range 6.2-62.8% and 32.1%, 7.7-56.8% respectively) which was significantly greater (P < 0.0001) than the spontaneous release (median 15.6%, range 4.1-33.4%), i.e. that in the absence of any stimulus. Substance P induced histamine release was via an energy dependent process and was blocked by preincubation with antimycin A. A significant correlation was observed between substance P induced release and spontaneous release but was not observed with A23187 induced release. Mast cell counts correlated significantly with substance P induced release but not with spontaneous or A23187 induced release. The substance P induced histamine secretion was elicited at similar concentrations to those used with rodent and human skin mast cells. Asthma is associated with increased numbers of mast cells which have both increased spontaneous and stimulated secretory responses. Thus, in vivo, the bronchoconstrictor action of substance P may in part result from activation of mast cells in the bronchial lumen.

Calcimycin↗
PubMed1994

Differential reactivity of human bronchoalveolar lavage mast cells to substance P.

Substance P (SP) stimulates human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, the ability of SP to stimulate human mast cells obtained at bronchoalveolar lavage (BAL) was examined. Routine BAL (n = 22) samples were obtained and histamine release experiments performed in a standard manner. Spontaneous histamine release was bimodally distributed (Group A, high spontaneous release/Group B, normal spontaneous release). Further, Group A had significantly elevated corrected SP-induced histamine release compared to Group B but the corrected calcium ionophore A23187-induced responses were similar. No differences were found in clinical history, age, lavage return or total cell numbers between groups. However, differential cell counts revealed significantly elevated mast cell numbers in Group A providing further evidence for altered mast cell responsivity associated with mast cell hyperplasia. In asthma, BAL mast cells have increased spontaneous and stimulated secretory responses; thus, in asthma SP may also stimulate pulmonary mast cells.

Aged↗
PubMed1994

Electronic cell counting to measure total cell numbers in bronchoalveolar lavage fluid.

Cell counting of bronchoalveolar lavage (BAL) fluid is performed manually in routine practice. This has both methodological and inherent errors; however, the accuracy and suitability of automated counting devices have been questioned. In this study, a Coulter Counter D Industrial model was calibrated and then used to measure the total cell count in unprocessed bronchoalveolar lavage fluid, and compared to a standard manual method. Bronchoalveolar lavage was performed on 34 patients undergoing routine bronchoscopy. An aliquot of unprocessed bronchoalveolar lavage fluid was taken for all counting procedures. Manual counts were performed blind by two experienced independent observers using improved Neubauer chambers. Electronic counting measured 1 ml aliquots suspended in 10 and 20 ml Isoton counting 0.5 and 1 ml duplicates. The correlation coefficients between electronic and manual counts were good. The coefficients of repeatability of electronic counts, for repeat counts, both on the same dilution (Intra-Coulter: 0.1 x 10(5) cells.ml-1) and different dilutions (Interdilution-Coulter: 0.48 x 10(5) cells.ml-1), were superior compared to those for repeat manual counts by the same observer (1.03 x 10(5) cells.ml-1), and counts between observers (1.82 x 10(5) cells.ml-1). This method offers a quick, precise and simple method for counting cells in unprocessed bronchoalveolar lavage fluid, which is both less labour intensive and subjective than manual counting.

Bronchoalveolar Lavage Fluid↗
PubMedDate not supplied

A retrospective survey of diagnosis and management of patients presenting with chronic cough to a general chest clinic.

Respiratory physicians often encounter patients with chronic cough. The evaluation and outcome of such patients by centres with established diagnostic protocols has been well described. By contrast, little is known about patients referred to general respiratory clinics where no such protocol exists. We describe the findings of a retrospective survey of all new patient referrals with chronic cough to a general respiratory clinic over a 12-month period. A diagnosis of asthma or chronic airflow obstruction was made in 43% of patients. Gastro-oesophageal reflux and postnasal drip syndrome, together accounting for over 60% of diagnoses in specialist clinics, were infrequently identified in our study (4% and 2% respectively). At follow-up, 43% of patients reported persistent symptoms, contrasting the excellent treatment response reported by specialist clinics. In general respiratory clinics where a specific diagnostic protocol is not in place, these differences in diagnosis and outcome may be due to inadequate investigation or may reflect a different patient population.

Adolescent↗