J. MacMahon

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.

Impact of Cough Across Different Chronic Respiratory Diseases: Comparison of Two Cough-Specific Health-Related Quality of Life Questionnaires

BACKGROUND Cough is a prominent symptom across a range of common chronic respiratory diseases and impacts considerably on patient health status. METHODS We undertook a cross-sectional comparison of scores from two cough-specific health-related quality of life (HRQoL) questionnaires, the Leicester Cough Questionnaire (LCQ), and the Cough Quality of Life Questionnaire (CQLQ), together with a generic HRQoL measure, the EuroQol. Questionnaires were administered to and spirometry performed on 147 outpatients with chronic cough (n = 83), COPD (n = 18), asthma (n = 20), and bronchiectasis (n = 26). RESULTS There was no significant difference in the LCQ and CQLQ total scores between groups (p = 0.24 and p = 0.26, respectively). Exploratory analyses of questionnaire subdomains revealed differences in psychosocial issues and functional impairment between the four groups (p = 0.01 and p = 0.05, respectively). CQLQ scores indicated that chronic coughers have more psychosocial issues than patients with bronchiectasis (p = 0.03) but less functional impairment than COPD patients (p = 0.04). There was a significant difference in generic health status across the four disease groups (p = 0.04), with poorest health status in COPD patients. A significant inverse correlation was observed between CQLQ and LCQ in each disease group (chronic cough r = - 0.56, p < 0.001; COPD r = - 0.49, p = 0.04; asthma r = - 0.94, p < 0.001; and bronchiectasis r = - 0.88, p < 0.001). There was no correlation between cough questionnaire scores and FEV(1) in any group, although a significant correlation between EuroQol visual analog scale component and FEV(1) (r = 0.639, p = 0.004) was observed in COPD patients. CONCLUSION Cough adversely affects health status across a range of common respiratory diseases. The LCQ and CQLQ can each provide important additional information concerning the impact of cough.

Oesophageal pH monitoring is of limited value in the diagnosis of “reflux-cough”

Reflux-cough is a diagnosis based on demonstrating both gastro-oesophageal reflux and a positive response to anti-reflux therapy. The authors sought to determine early and long-term response to therapy in patients with a “positive” 24 h oesophageal pH study, and identify any features which might predict response. Patients with chronic cough were recruited from July 1998 to July 2002. Those with a positive pH study were given dietary advice and an 8-week trial of omeprazole (20 mg b.i.d.). Response was judged after 8 weeks (clinical follow-up), and at long-term follow-up (telephone questionnaire). A total of 146 patients underwent pH monitoring with 82 (56.2%) “positive” studies. Follow-up data was available in 60 patients, with 49 receiving anti-reflux therapy, of which 20 (40.8%) reported a positive treatment response. At long-term follow-up (median 30 months), there was a significantly lower response (14 out of 49, 28.5%), with no significant difference in either acid exposure times (distal/proximal) or symptom correlation between responders and nonresponders at early or long-term follow-up. In conclusion, despite “positive” pH studies, over half of the patients (55.1%) failed torespond to therapy. No features on pH monitoring accurately predicted response. Short-term response did not predict long-term response. The precise role for pH monitoring in the assessment of chronic cough remains to be defined.

Prevalence of psychomorbidity among patients with chronic cough.

BackgroundChronic cough may cause significant emotional distress and although patients are not routinely assessed for co-existent psychomorbidity, a cough that is refractory to any treatment is sometimes suspected to be functional in origin. It is not known if patients with chronic cough referred for specialist evaluation have emotional impairment but failure to recognise this may influence treatment outcomes. In this cross-sectional study, levels of psychomorbidity were measured in patients referred to a specialist cough clinic.MethodsFifty-seven patients (40 female), mean age 47.5 (14.3) years referred for specialist evaluation of chronic cough (mean cough duration 69.2 (78.5) months) completed the Hospital Anxiety and Depression (HAD) scale, State Trait Anxiety Inventory (STAI) and the Crown Crisp Experiential Index (CCEI) at initial clinic presentation.Subjects then underwent a comprehensive diagnostic evaluation, after which they were classified as either treated cough (TC) or idiopathic cough (IC). Questionnaire scores were compared between TC (n = 42) and IC (n = 15).ResultsUsing the HAD scale, 33% of all cough patients were identified as anxious, while 16% experienced depression. The STAI scores suggested moderate or high trait anxiety in 48% of all coughers. Trait anxiety was significantly higher among TC (p < 0.001) and IC patients (p = 0.004) compared to a healthy adult population. On the CCEI, mean scores on the phobic anxiety, somatisation, depression, and obsession subscales were significantly higher among all cough patients than the published mean scores for healthy controls. Only state anxiety was significantly higher in IC patients compared with TC patients (p < 0.05).ConclusionPatients with chronic cough appear to have increased levels of emotional upset although psychological questionnaires do not readily distinguish between idiopathic coughers and those successfully treated.

Sensory neuropeptides induce histamine release from bronchoalveolar lavage cells in both nonasthmatic coughers and cough variant asthmatics

Sensory neuropeptides have been suggested to play a role in the pathogenesis of a number of respiratory diseases including asthma and chronic non‐productive cough.

Cytokine concentrations and neutrophil elastase activity in bronchoalveolar lavage and induced sputum from patients with cystic fibrosis, mild asthma and healthy volunteers

BACKGROUND Induced sputum (IS) has been proposed as a non-invasive alternative to bronchoalveolar lavage (BAL) for the assessment and monitoring of airways inflammation. The aim of this study was to compare both methods in patients with cystic fibrosis (CF). The possible differences between subjects with CF, mild asthma and healthy volunteers (HV) was also assessed. METHOD In a single centre, randomised, two way crossover study, 11 patients with CF, 9 mild asthmatics (MA) and 11 HV underwent BAL and hypertonic saline induction on consecutive days. Free neutrophil elastase (NE), neutrophil elastase/alpha(1)-anti-trypsin complex (NE-AAT), tumour necrosis factor receptor (p55) and interleukin-8 (IL-8) were measured in cell free supernatants. RESULTS Three CF patients reported serious adverse events following BAL. NE was usually undetectable in both IS or BAL samples and NE-AAT concentrations did not differ consistently between the two sampling methods. IL-8 and p55 levels in the CF patients tended to be higher in IS samples compared with BAL samples (median 19,860 vs. 3,855 pg/ml and 2.55 vs. 0.29 ng/ml, respectively). There was a significant difference in mean p55 concentrations between CF, MA and HV in IS samples (P=0.003) but not in BAL samples (P=0.36). The difference in mean IL-8 concentrations in IS samples between subject groups was statistically different (P=0.023). CONCLUSIONS IS samples can be safely obtained from CF patients. Analysis of IS samples can help to characterize the inflammatory process in the airways of CF patients. The serious adverse events following BAL in 3 CF patients highlight an inherent risk associated with this procedure.

Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland).

Background Environmental, cultural and health care differences may account for variation among countries in the prevalence of asthma and respiratory symptoms in teenagers.

The modulatory effects of WE-14 on histamine release from rat peritoneal mast cells

peritoneal mast cells P. Forsythe, W. J. Curry , C. F. Johnston, P. Harriott , J. MacMahon and M. Ennis Department of Clinical Biochemistry, Institute of Clinical Science, The Queen’s University of Belfast, Grosvenor Road, Belfast BT12 6BJ, UK 2 Department of Medicine, Institute of Clinical Science, The Queen’s University of Belfast, Grosvenor Road, Belfast BT12 6BJ, UK School of Biology and Biochemistry, The Queen’s University of Belfast, Lisburn Road, Belfast BT9 7BL, UK Department of Respiratory Medicine, Belfast City Hospital, Lisburn Road, Belfast BT9 7BA, UK

Cost minimisation analysis of provision of oxygen at home: are the Drug Tariff guidelines cost effective?

Abstract Objectives: To determine the level of oxygen cylinder use at which it becomes more cost effective to provide oxygen by concentrator at home in Northern Ireland, and to examine potential cost savings if cylinder use above this level had been replaced by concentrator in 1996. Design: Cost minimisation analysis. Setting: Area health boards in Northern Ireland. Main outcome measures: Cost effective cut off point for switch to provision of oxygen from cylinder to concentrator. Potential maximum and minimum savings in Northern Ireland (sensitivity analysis) owing to switch to more cost effective strategy on the basis of provision of cylinders in 1996. Results: In Northern Ireland it is currently cost effective to provide oxygen by concentrator when the patient is using three or more cylinders per month independent of the duration of the prescription. More widespread use of concentrators at this level of provision is likely to lead to a cost saving. Conclusions: The Drug Tariff prescribing guidelines, advocating that provision of oxygen by concentrator becomes cheaper when 21 cylinders are being used per month—are currently inaccurate in Northern Ireland. Regional health authorities should review their current arrangements for provision of oxygen at home and perform a cost analysis to determine at what level it becomes more cost effective to provide oxygen by concentrator. Key messages The current Drug Tariff prescribing guidelines are not cost effective for provision of oxygen at home in Northern Ireland Individual prescriptions detailing frequency of usage and delivery costs should be recorded A switch to a more cost effective strategy is likely to result in a cost saving Regional health authorities should examine current arrangements for provision of oxygen at home and should perform cost analyses

Common causes and current guidelines

Chronic cough is a common and disabling symptom. Recent guidelines have attempted to provide direction in the clinical management of cough in both primary and secondary care. They have also provided a critical review of the available literature and identified gaps in current knowledge. Despite this they have been criticized for a reliance on a low quality evidence base. In this review, we summarize the current consensus on the clinical management of chronic cough and attempt to rationalize this based on recent evidence. We have also provided an overview of the likely pathophysiological mechanisms responsible for cough and highlighted areas, where knowledge deficits exist and suggest directions for future research. Such progress will be critical in the search for new and effective treatments for cough. Chronic Respiratory Disease 2007; 4: 215—223