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author:("warshaw, M J")
2.  Targeting of dornase alpha therapy in adult cystic fibrosis. 
Although dornase alpha (recombinant human DNase) can thin the viscid pulmonary secretions of cystic fibrosis (CF), clinical trials in groups of unselected patients have shown only modest average improvements in pulmonary function. The product is very expensive, so in conjunction with purchasers we designed selection criteria and a protocol for a 2-week trial to target CF individuals who might gain most benefit. Treatment was to be continued in those showing > or = 10% improvement in pulmonary function. Those who had a trial of dornase alpha were followed up for 2 years. Of 25 patients who had a 2-week trial of dornase alpha, 17 met the criteria for continuation (average gain in forced expiratory volume 37%). The 11 of these who were still alive at 2 years had a greater initial average FEV1 improvement than those who had died (45% versus 22%), and still had an average improvement of 31% at 2 years. The 8 patients who did not meet the criteria for continuation were older and had required fewer intravenous antibiotic courses. All these were alive at 2 years with unchanged clinical indices. This method of selection for dornase alpha treatment allows targeting to those who gain most benefit without disadvantaging the remaining patients. Furthermore, production of such guidelines in conjunction with purchasers obviates funding difficulties and allows rational prescribing.
PMCID: PMC1296808  PMID: 9771494
3.  Prevalence and mechanisms of gastro-oesophageal reflux in adult cystic fibrosis patients. 
Gastro-oesophageal reflux (GOR) occurs frequently in children with cystic fibrosis (CF) but has not been studied in adult CF. We surveyed such symptoms by structured questionnaire in 50 adult CF patients (mean age 26 years, range 16-50; 24 male) and performed oesophageal manometry and 24-hour pH recording in 10 who had reflux symptoms (mean age 28 years, range 21-35; 8 men). 47 patients (94%) had upper gastrointestinal symptoms: 40 (80%) heartburn (27 worse when supine); 26 (52%) regurgitation; and 28 (56%) dyspepsia. At oesophageal manometry, lower oesophageal sphincter barrier pressure (LOSBP) was subnormal in 6 of the 10 patients and 3 had uncoordinated peristalsis in the mid oesophagus. 8 patients had raised DeMeester scores, indicating significant GOR. Those patients with a LOSBP < 5mm Hg had a higher DeMeester score (mean 81.0, range 47.9-128.8) than the patients with a normal LOSBP (26.9, 8.7-56.5; p < 0.002). These results show that adult CF patients have high rates of GOR symptoms, diminished LOSBP, and acid reflux.
PMCID: PMC1296415  PMID: 9536132
4.  Tracheal microaspiration in adult cystic fibrosis. 
Gastro-oesophageal reflux (GOR) has been implicated in the aetiology of lung disease. Cystic fibrosis (CF) patients have a high incidence of GOR symptoms with demonstrable episodes of oesophageal acidification. We studied 24-hour ambulatory tracheal and oesophageal pH in 11 CF patients with GOR symptoms to identify any episodes of tracheal acidification and define their temporal relation to oesophageal reflux and respiratory symptoms. 8 patients had evidence of significant GOR (DeMeester score mean 58; range 17-107) and in 6 it was gross (DeMeester score > 30). 4 patients had tracheal acidification (defined as tracheal pH < 5.5): all had greatly raised DeMeester scores. Two patterns of lowered tracheal pH were seen: a gradual drift downwards of tracheal pH to < 5.5 which recovered slowly, and an acute fall in tracheal pH to < 5.5 with rapid recovery. Only one patient had a fall in peak expiratory flow in conjunction with a decline in tracheal pH, and no association was found between the presence of tracheal microaspiration and pulmonary function. We conclude that tracheal acidification occurs in adult CF patients with GOR.
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PMCID: PMC1296416  PMID: 9536133
5.  Hypoxia in patients with acute hemiplegia. 
Sixteen patients with an early dense hemiplegia due to cerebrovascular accidents were shown to have a greater degree of hypoxia than 16 matched control patients. The patients with hemiplegia had a reflex compensatory fall in arterial carbon dioxide tensions (PaCO2) with possible reduction in cerebral blood flow. Oxygen treatment led to an increase in PaCO2 in the patients with hemiplegia, but the increase in oxygen tensions in these patients was significantly less than that in the control group, suggesting increased pulmonary shunting as the cause for the hypoxia. Oxygen treatment may improve cerebral blood flow and oxygenation and have a useful role in the early management of patients with a dense hemiplegia.
PMCID: PMC1444120  PMID: 6418296
6.  Treatment of large airway obstruction in lung cancer using expandable metal stents inserted under direct vision via the fibreoptic bronchoscope. 
Thorax  1996;51(3):248-252.
BACKGROUND: Self-expanding metal stents have been used successfully to overcome large airway obstruction due to malignant pulmonary disease. The technique has been modified to place stents under direct vision using the fibreoptic bronchoscope. The effect of this procedure on lung function and patient well being was investigated in a large series of patients. METHODS: Fifty six patients with malignant tracheobronchial tumours were treated for symptoms of life threatening airways obstruction or collapse of a lung by the insertion of an expandable metal stent(s) under local anaesthetic using a fibreoptic bronchoscope. All had inoperable cancer and 33 had relapsed after or failed to respond to radiotherapy, chemotherapy, or surgery. Forty seven had primary bronchial carcinomas and nine had metastases from other tumour sites. All but two patients had the stents inserted at one sitting. Measurements were performed in most of the patients before and after stenting and included objective measures (pulmonary function tests, arterial blood gas tensions) and non-objective measures (patient well being, performance status). RESULTS: Overall, 77% of patients showed symptomatic improvement. In those patients in whom measurements were performed two thirds showed improvement in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR) and arterial oxygen tension (PaO2). Medical Research Council dyspnoea score (MRC), Karnofsky, and visual analogue scores (for both breathing and well being) improved in 81% of patients. There were no perioperative deaths. Fifty one patients have died since the procedure with a mean survival of 77 days (range 1-477), and five patients are still alive after a mean of 207 days (range 135-274). CONCLUSIONS: In suitable patients with either extraluminal or intraluminal tumour, or both, the insertion of expandable metal stents using a fibreoptic bronchoscope and local anaesthetic is a valuable addition to other palliative therapies in the treatment of lung cancer.
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PMCID: PMC1090633  PMID: 8779125
7.  A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma. 
Thorax  1992;47(6):446-450.
BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.
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PMCID: PMC463810  PMID: 1496504
8.  Bacterial colonisation of humidifier attachments on oxygen concentrators prescribed for long term oxygen therapy: a district review. 
Thorax  1991;46(4):257-258.
A microbiological survey was undertaken on the eight patients in the Liverpool District who have a humidifier attachment on their oxygen concentrator. All but one of the humidifiers were contaminated with potentially pathogenic bacteria.
PMCID: PMC463091  PMID: 2038734
9.  Bacterial Diversity in Cases of Lung Infection in Cystic Fibrosis Patients: 16S Ribosomal DNA (rDNA) Length Heterogeneity PCR and 16S rDNA Terminal Restriction Fragment Length Polymorphism Profiling 
Journal of Clinical Microbiology  2003;41(8):3548-3558.
The leading cause of morbidity and mortality in cystic fibrosis (CF) patients stems from repeated bacterial respiratory infections. Many bacterial species have been cultured from CF specimens and so are associated with lung disease. Despite this, much remains to be determined. In the present study, we characterized without prior cultivation the total bacterial community present in specimens taken from adult CF patients, extracting DNA directly from 14 bronchoscopy or sputum samples. Bacterial 16S ribosomal DNA (rRNA) gene PCR products were amplified from extracted nucleic acids, with analyses by terminal restriction fragment length polymorphism (T-RFLP), length heterogeneity PCR (LH-PCR), and sequencing of individual cloned PCR products to characterize these communities. Using the same loading of PCR products, 12 distinct T-RFLP profiles were identified that had between 3 and 32 T-RFLP bands. Nine distinct LH-PCR profiles were identified containing between one and four bands. T-RFLP bands were detected in certain samples at positions that corresponded to pathogens cultured from CF samples, e.g., Burkholderia cepacia and Haemophilus influenzae. In every sample studied, one T-RFLP band was identified that corresponded to that produced by Pseudomonas aeruginosa. A total of 103 16S rRNA gene clones were examined from five patients. P. aeruginosa was the most commonly identified species (59% of clones). Stenotrophomonas species were also common, with eight other (typically anaerobic) bacterial species identified within the remaining 17 clones. In conclusion, T-RFLP analysis coupled with 16S rRNA gene sequencing is a powerful means of analyzing the composition and diversity of the bacterial community in specimens sampled from CF patients.
doi:10.1128/JCM.41.8.3548-3558.2003
PMCID: PMC179861  PMID: 12904354
11.  Autonomic dysfunction in cystic fibrosis. 
Journal of the Royal Society of Medicine  2003;96(Suppl 43):11-17.
PMCID: PMC1308782  PMID: 12906320
12.  Posture and cystic fibrosis. 
Journal of the Royal Society of Medicine  2003;96(Suppl 43):18-22.
PMCID: PMC1308783  PMID: 12906321
13.  Cardiac arrhythmias during acute exacerbations of chronic airflow limitation: effect of fall in plasma potassium concentration induced by nebulised beta 2-agonist therapy. 
Postgraduate Medical Journal  1989;65(765):449-452.
The effect on cardiac rhythm of the fall in plasma potassium concentration induced by nebulised beta2-agonist therapy was studied in 20 patients admitted to hospital with an acute exacerbation of their reversible chronic airflow limitation. Arrhythmias considered serious or potentially life-threatening were recorded in 13 patients (65%). However, there was no significant increase in these arrhythmias in the hour following administration of nebulised beta2-agonist despite a significant fall in plasma potassium concentration during this period.
PMCID: PMC2429413  PMID: 2602234
14.  Prescription of oxygen concentrators for long term oxygen treatment: reassessment in one district. 
BMJ : British Medical Journal  1988;297(6655):1030-1032.
When oxygen concentrators became available on form FP10 in 1985 the Department of Health and Social Security issued clear guidelines for their prescription for long term treatment. Reassessment of those patients prescribed a concentrator in one district showed that 29 out of 61 patients did not fulfil these criteria. Furthermore, in only 28 cases was the daily use of the machine appropriate, though this did not reflect poor patient cooperation but was a result of inadequate prescribing instructions. In addition, 12 out of 54 patients continued to smoke. Overall, in only 18 of the 61 cases was both the prescription appropriate and the concentrator properly used. These results suggest a need for better cooperation between general practitioner and hospital in the initial assessment of patients for long term oxygen treatment and better education of both doctor and patient in the use of oxygen concentrators.
PMCID: PMC1834827  PMID: 3142600

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