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Khalid, Saifudin. "Inhalational cough challenges in the assessment of cough." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/inhalational-cough-challenges-in-the-assessment-of-cough(8788e20e-3f76-4600-bdc1-e9bee31b5c01).html.
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Introduction: Cough is the commonest reason for which medical advice is sought. In assessment of chronic cough and in developing anti-tussive medications, inhalational cough challenges with capsaicin and citric acid are commonly employed. However the ability of these inhalational cough challenges to distinguish health and disease is not clear and it is not known which end point is best in making such assessments. Methods: Subjects belonging to five different categories (healthy volunteers, subjects with COPD, asthma, healthy current smokers and chronic cough) were compared with each another by using the standard cough challenges employing Capsaicin and Citric acid and also by using newer inhalational cough challenge agents such as prostaglandin E2 and bradykinin. In addition adaptation to repeated inhalations of tussive agents was also assessed. The relationship between the cough reflex sensitivity as gauged by using inhalational cough challenge tests and objective cough recording was explored in all five groups. Finally the change in C5 in Capsaicin evoked cough by using a substance to block TRPV1 channel and its effect on objective cough recording was assessed in subjects with chronic cough. Results: Different tussive agents have different abilities to distinguish between different diagnostic categories and a combination of inhalational cough challenge tests have a better accuracy of predicting diagnostic groups as compared to one on its own. There are significant differences in the rates of adaptation to repeated inhalations of PGE2 and there is a significant reduction in cough response over period of time in all disease groups. Using the TRPV1 antagonist resulted in a modest increase in the Log C5 concentration of capsaicin but this was not matched by a change in objective cough recording or CQLQ scores. Conclusions: The different abilities of tussive agents to distinguish between different diagnostic categories suggest that the information conveyed by the one inhalational cough challenge test is different from that by another test. The choice of the inhalational cough challenge test should therefore depend on which groups are included in the study. There was no significant difference in the rate of adaptation to prolonged challenge with citric acid or capsaicin and no significant correlation of the magnitude of adaptation with objective cough recording suggesting that this is unlikely to be responsible for the increased cough rates seen in diseases such as chronic cough, COPD or asthma. The TRPV1 antagonist did not result in a significant change in objective cough recording or CQLQ scores. The change in C5 with the TRPV1 antagonist was however modest and this may be reason for this study failing to show a relationship between these different measures.
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Hassan, H., Gayatri Jaishankar, and Demetrio Macariola. "The "Non" Whooping Cough." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etsu-works/8861.
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Pillay, Victoria. "A systematic review of the symptomatic treatment of the cough in whooping cough." Master's thesis, University of Cape Town, 2002. http://hdl.handle.net/11427/8789.
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Includes bibliographical references.Background: There are between 20 - 40 million cases of whooping cough annually world-wide, 90% of which occur in developing countries, resulting in an estimated 200 - 300 O00 fatalities each year. Much of the morbidity is due to the paroxysmal cough. Corticosteroids, salbutamol (a β₂- adrenergic stimulant), and pertussis-specific immunoglobulin have been proposed as standard treatment for the cough. Antihistamines have also been administered. No systematic review of the effectiveness of any of these interventions or others has been performed. Objective: in this systematic review we aim to assess the effectiveness of interventions used to reduce the severity of the coughing paroxysms in whooping cough in children and adults. Selection criteria: Randomised and quasi randomised controlled trials of any intervention that reduced the severity of the coughing paroxysms in whooping cough; excluding antibiotics and vaccines. Study selection: All interventions aimed at reducing the severity of the coughing paroxysms in children or adults with whooping cough with any of the following outcome measures met inclusion criteria for the review; i) frequency of paroxysms of coughing (primary outcome), ii) frequency of vomiting, iii) frequency of whoop, iv) frequency of cyanotic spells, v) development of serious complications, vi) mortality from any cause, vii) side effects due to medication, viii) admission to hospital, and ix) duration of hospital stay. Search strategy: We searched the Cochrane Controlled Trials register, Acute Respiratory infectious Disease Group Specialised Trials register, MEDLINE, LILACS, scanned reference lists of identified trials, contacted authors of identified trials and the relevant pharmaceutical companies. Data collection and analysis: Studies were selected, quality assessed and data extracted by two reviewers independently. Results: Nine studies satisfied the inclusion criteria but four had insufficient data for further meta-analysis of our pre-specified outcomes. Studies were old and poorly reported. The largest study had a total sample size of 49 and the smallest study nine. All studies were performed in industrialised settings. Eligible studies assessed diphenhyramine, pertussis immunoglobulin, dexamethasone and salbutamol. No statistically significant benefit was found for any of the interventions. Diphenhydramine was associated with a mean increase of 1.90 coughing spells per 24 hours [95%Cl - 4.66; 8.46] and pertussis immunoglobulin a mean decrease in hospital stay of 0.70 days [95% Cl -3.79; 2.39]. and a mean reduction of 3.10 whoops per 24 hours [95% CI - 6.22; 0.02]. Dexamethasone resulted in a mean decrease in hospital stay of 3.45 days [95% Cl - 15.34; 8.44] and salbutamol in a weighted mean decrease in coughing paroxysms of 0.95 per 24 hours [95% Cl - 6.21; 4.31]. Reviewers' conclusion: Although assessments have been performed on a whole range of interventions, including diphenhyramine, pertussis immunoglobulin, dexamethasone and salbutamol, insufficient evidence exists to draw conclusions about the effects of any of them.
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Mason, Nicholas. "Mechanisms of altitude-related cough." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209711.
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The original work presented in this thesis investigates some of the mechanisms that may be responsible for the aetiology of altitude-related cough. Particular attention is paid to its relationship to the long recognised, but poorly understood, changes in lung volumes that occur on ascent to altitude. The literature relevant to this thesis is reviewed in Chapter 1.Widespread reports have long existed of a debilitating cough affecting visitors to high altitude that can incapacitate the sufferer and, on occasions, be severe enough to cause rib fractures (22, 34, 35). The prevalence of cough at altitude has been estimated to be between 22 and 42% at between 4200 and 4900 m in the Everest region of Nepal (10, 29). Traditionally the cough was attributed to the inspiration of the cold, dry air characteristic of the high altitude environment (37) but no attempts were made to confirm this aetiology. In the first formal study of cough at high altitude, nocturnal cough frequency was found to increase with increasing altitude during a trek to Everest Base Camp (5300 m) and massively so in 3 climbers on whom recordings were made up to 7000 m on Everest (8). After 9 days at 5300 m the citric acid cough threshold, a measure of the sensitivity of the cough reflex arc, was significantly reduced compared with both sea level and arrival at 5300 m.
During Operation Everest II, a simulated climb of Mount Everest in a hypobaric chamber, the majority of the subjects were troubled above 7000 m by pain and dryness in the throat and an irritating cough despite the chamber being maintained at a relative humidity of between 72 and 82% and a temperature of 23ºC (18). This argued against the widely held view that altitude-related cough was due to the inspiration of cold, dry air.
In the next major hypobaric chamber study, Operation Everest III, nocturnal cough frequency and citric acid cough threshold were measured on the 8 subjects in the study. The chamber temperature was maintained between 18 and 24ºC and relative humidity between 30 and 60% (24). This work is presented in Chapter 2 and, demonstrated an increase in nocturnal cough frequency with increasing altitude which immediately returned to control values on descent to sea level. Citric acid cough threshold was reduced at 8000 m compared to both sea level and 5000 m values. Changes in citric acid cough threshold at lower altitudes may not have been detected because of the constraints on subject numbers in the chamber. The study still however demonstrated an increase in clinical cough and a reduction in the citric acid cough threshold at extreme altitude, despite controlled environmental conditions, and thus refuted the long held belief that altitude-related cough is solely due to the inspiration of cold, dry air.
If altitude-related cough is not simply due to the inspiration of cold, dry air, other possible aetiologies are:
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Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
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Dixon, Nicola Jane. "The psychology of chronic cough." Thesis, University of Hull, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395657.
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Yousaf, Nadia. "Cough in health and disease." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/28114.
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Cough is a common symptom of both acute and chronic respiratory illness. It is poorly understood and treatment options are sparse. One reason is that there are few validated objective measures of cough frequency and severity. In this thesis I have further validated the Leicester Cough Monitor, an automated cough detection system capable of detecting coughs over 24 hours. I have demonstrated that automated cough numbers were similar to those derived from the gold standard of manual counting in healthy adults and in patients with respiratory disease. Cough frequency was then measured using the Leicester Cough Monitor and was almost 16 fold higher in patients with respiratory diseases compared to healthy controls. In the population as a whole there was a correlation between cough frequency and the induced sputum neutrophil count. I then conducted a randomised, placebo controlled, double blind, parallel group trial of low dose erythromycin taken daily for 3 months in 30 patients with unexplained chronic cough. Active treatment was associated with a reduction in the sputum neutrophil count but no difference in cough counts or other measures of cough severity. Also, there is no information on the natural history of unexplained chronic cough. In a longitudinal study of 42 patients with unexplained chronic cough followed up for at least 7 years, I found that cough, measure by the cough visual analogue score, improved in 25 percent. Unexpectedly, patients had an abnormally rapid fall in FEV1, whether cough improved or not. Finally, the assessment of health related quality of life is important in people with acute cough in order to evaluate potential therapies. I have shown that that the minimal important clinical difference in the Leicester Cough Questionnaire for those with acute cough is 2.5 and this will aid in the interpretation of treatment trials.
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Kelsall, Angela. "Respiratory physiology in chronic cough." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491479.
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Introduction: Varying methods of cough quantification have been used to describe cough frequency, although there is no consensus which method best relates to subjective rating of cough. With increased availability of semi-automated cough recording devices, the capability to carryout anti-tussive studies is greatly increased. However, there is no data available describing the magnitude of change in cough frequency necessary to provide therapeutic benefit. Female patients are over represented in specialist cough clinics. There is little data describing pulmonary function and airway inflammation in phenotyped patients and how these measures may relate to objectively measured cough. Airway inflammation isa common feature of chronic cough, regardless of the trigger for cough. The repetitive mechanical insult of the act of coughing may be responsible for the presence ofthis inflammation. Methods: 100 patients with unexplained chronic cough under went full diagnostic testing in order to determine potential triggers for cough. Procedures included pulmonary function testing; (spirometry, eND, EBC pH, BHR, Cough challenge, induced sputum, objective and subjective cough monitoring), Bronchoscopy, 24 hour impedance monitoring with simultaneous cough monitoring, Gastroscopy and ENT. A subset of cough recordings were quantified in cough sounds, cough seconds and cough epochs to determine the best way to quantify cough. 20 healthy volunteers performed voluntary coughing manoeuvres to determine the acute effects of coughing on airway function and inflammation. Results: Cough sounds and seconds correlate moderately with subjective and QDL . methods. Patients reported a reduced cough frequency whilst undergoing impedance testing; a reduction of33% was seen although patients were unable to quantify the scale of change. Female patients coughed substantially more than male patients, with the largest difference seen at night. Cough frequency was predicted by gender, C5 and age. Cough frequency was not related to a specific trigger for cough. Reduced small airway flows were seen that were independent of BHR. Prominent airway neutrophilia was seen regardless of the trigger for cough. Acute changes in eND and EBC were seen after short periods ofvoluntary coughing. Sputum inflammatory mediator levels showed huge variability and did not change as a result of coughing. Bronchodilation ofthe small airways was also seen after coughing. Conclusion: The use of objective cough monitoring has enabled me for the first time to describe the most appropriate current methods of cough quantification and to demonstrate the magnitude ofreduction in cough frequency that is appreciated by -patients.-I-havereportedimportant significant genderdifferences in cough frequency and shown that cough frequency is predicted not only by gender but also age and cough reflex sensitivity showing important implications for underlying mechanisms of chronic cough. I have also shown for the first time that pulmonary function measures are reduced in patients without indication of asthma. The mechanical act of coughing causes acute bronchodilation of small airways and reduces eND and EBC pH.
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Marsden, Paul Anthony. "Cough, asthma and airways inflammation." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516825.
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Rationale Cough is an important symptom in asthma. In addition, cough is both troublesome to patients and may be important in the development of more severe disease. Moreover, it is a key symptom in the diagnosis of asthma, according to international guidelines. Little is known regarding the mechanism of cough in asthma. Until now, subjective measures of cough have been used in mechanistic and therapeutic studies relating to both cough in asthma and chronic cough. There is no published literature documenting cough rates in asthma or the relationship between cough rates and both subjective measures of cough and asthma control. In addition, the relationship between objective cough rates and airway inflammation, and the effects of cough on airway function and inflammation is unknown. Methods A series of studies was designed and carried out to answer the above questions. Firstly, a cross sectional study examining the relationships between objective and subjective measures of cough in classical asthma (CA), secondly a longitudinal study examining the relationship between cough rates and CA control and thirdly a cross-sectional study examining the effects of voluntary cough on airway function and inflammation. Results There was a poor correlation between objective and subjective measures of cough in CA. Cough-related quality of life correlated most closely with cough rates. Traditional measures of CA (e.g. spirometry) poorly reflected cough rates. Objective cough rates and sputum eosinophils were predictive of CA control as defined by ACO. Objective cough rates did not reflect sputum inflammatory cell count or mediators. Voluntary cough induced small changes in peak flow in mildmoderate CA and small changes in sputum ECP that were not reflected by changes in sputum eosinophils. Conclusions Subjective measures of cough in asthma are poor substitutes for objective cough rates. When designing studies for cough in asthma, both objective cough rates and cough-related quality of life should be incorporated. Objective cough rates reflect asthma control (independent of airway inflammation) more closely than traditional measures of asthma. Airway inflammation does not appear to directly reflect cough rates. In addition, short bouts of coughing in mildmoderate asthma induce neither significant changes in airway function nor airway inflammation.
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McGuinness, Kevin. "Cough detection. a physiological approach." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528494.
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Elghamoudi, Deblej. "Objective cough monitoring in children." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/objective-cough-monitoring-in-children(e3d822f0-d1b1-4056-8f98-1b6dd634c47f).html.
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Background: Cough is extremely common in childhood and a tool to objectively measure cough frequency would be clinically beneficial. To date paediatric cough monitoring systems have relied on manual cough counting which is time consuming and costly. The VitaloJAK⢠(Vitalograph, UK) is a custom built 24hr semi-automated cough monitoring device that has been used successfully to quantify cough in adults. This thesis consists of a series of studies using the VitaloJAK⢠monitor system in children. Methods: Firstly, we tested the feasibility of using the VitaloJAK⢠for 24 hr cough recordings in children and tested existing compression software for cough quantification. The VitaloJAK⢠system was then used to to assess and compare the cough frequency, variation and circadian distribution of cough in children with asthma, CF, and PCD during stable periods of disease and during an exacerbation. Finally, we used modelling to assess whether cough events are random events, or are clustered in time; the time intervals between coughs for each patient were calculated and fitted to an exponential model of random recurrences and a Weibull model for clustered recurrences. Results: The majority of children were able to wear the monitor for almost 24 hours without too much difficulty; overall, children wore the monitor for a median of 22.25 hours (0.38 â 24hrs). Using the compression software, a median of 100% (91-100) of coughs was retained and 24-hour records were reduced down to around 10% of their original size. There was no significant difference in cough frequency between the three disease groups. The median (range) cough frequency per hour was 3 (0.2 to 18) coughs/hour (c/h), 4 (0.5 to 37) c/h, and 4 (0.5 to 27) c/h for asthma, CF, and PCD groups respectively (p=0.3). Cough frequency in children was significantly greater during the day and reduced during sleep in all disease groups. There was a significant difference in the 24-hour cough frequency between the exacerbation and stable asthma group (median 11 (0-27) vs. 3 (0-5), p=0.004). The 24-hour pattern revealed a substantial variability in peak timing of cough in each respiratory disease. Children with asthma peaked in the early evening, those with CF in the morning, and those with PCD in the afternoon. No difference was found in the circadian cough rate, when divided into 6 4-hour time periods, either between the three diseases (p=0.18) or between stable and exacerbation phases among the asthmatic children (p=0.14). A significant difference was seen in the 24-hour total cough frequency between asthmatic children (median 4c/h; range 1-18) and adults (median 1 c/h; range 0.3-16); p=0.001. The temporal pattern of recurrence of cough events is non-randomly distributed over time, and this was best described by the Weibull model in the majority of the 24hr cough, day-time cough and night-time cough recordings in children and adults. The cough events appear to cluster together in time, with the probability of a second cough being initially high and decreasing with time. Conclusion: This thesis has demonstrated that the VitaloJAK⢠semi-automated cough monitor provides an accurate estimate of cough frequency in children (sensitivity 100%) while significantly reducing the time required for analysis. A substantial variability in the timing of peak cough frequency exists in each respiratory disease and this might reflect different mechanisms of cough in each disease. Sleep appears to significantly reduce cough in all the diseases studied, both when disease is stable and exacerbating. In both asthmatic children and adults, the recurrence pattern of coughs is clustered and can be described by a Weibull distribution. This work has set a foundation for further investigation of the cough frequency and 24 hour cough circadian patterns in children.
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Blackwelder, Reid B. "Primary Care Approach to Cough." Digital Commons @ East Tennessee State University, 2003. https://dc.etsu.edu/etsu-works/6994.
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Lee, Kai Kong. "Objective measures of cough severity." Thesis, King's College London (University of London), 2014. http://kclpure.kcl.ac.uk/portal/en/theses/objective-measures-of-cough-severity(5fd78f7a-7458-41ec-8d58-c804b3d483b6).html.
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Cough is a common complaint that results in significant morbidity and impairment in quality of life. The assessment of cough severity is central to the diagnosis and clinical management of cough. The aim of this thesis was to evaluate objective measures of cough frequency and cough intensity in patients with acute and chronic cough. 24-hour cough frequency was investigated in a longitudinal observational study of 33 healthy subjects with acute cough. At baseline, 24-hour cough frequency was elevated and was associated with impaired health related quality of life. Cough frequency improved significantly over the 8-day study period. The minimal clinically important difference in cough frequency was determined as a 54% change from baseline. The sample sizes required for clinical trials to use cough frequency as a primary endpoint were calculated using this data. A second study of cough frequency was undertaken in 100 patients with chronic cough to investigate whether short duration recordings (1-6 hours) were comparable to 24-hours. Cough frequency obtained from short recordings were strongly correlated with 24-hour cough frequency (ρ=0.77 to 0.93), but those less than 4 hours were limited by weak relationships with subjective measures of cough. 4-hour cough frequency was found to be responsive to improvements in cough severity following trials of therapy, supporting its feasibility as a tool for assessing outcomes in chronic cough. The intensity of cough is an important determinant of global cough severity, but few studies have assessed cough intensity objectively in patients with chronic cough. The intensity of voluntary, induced and spontaneous cough was investigated in 28 patients with chronic cough and 21 healthy controls. Oesophageal pressure (Poes), gastric pressure (Pga) and peak cough flow rate (PCFR) during maximum voluntary cough were significantly greater in patients with chronic cough compared with controls when taking into account the preceding inspired volume. There was no difference in expiratory muscle strength or degree of abdominal muscle activation between patients and controls but the compression phase duration (CPD) was increased in female patients with cough compared to controls (mean ± SD CPD 0.50 ± 0.22 vs. 0.28 ± 0.17 seconds; p=0.007). Cough intensity during spontaneous cough was comparable to induced cough, but less than maximum voluntary cough intensity. Poes, Pga and PCFR were closely correlated with cough intensity visual analogue score (ρ=0.86 to 0.90), suggesting that these indices are important to subjective perception of cough intensity. Cough sound is a potential measure of cough intensity, but it has not been validated against physiological measures of cough intensity. The relationship between a range of cough sound parameters and PCFR and Poes were investigated in 17 patients with chronic cough and 15 healthy controls. Cough sound power and energy were found to correlate most strongly with PCFR (ρ=0.82 to 0.88) and Poes (ρ=0.85 to 0.89). The relationships between sound and PCFR or Poes were similar for sound analysed from a fixed 0.5-second time-window and from time-windows that were manually marked by cough phase, supporting the potential for future automated analysis. Sound power and energy were highly repeatable measures (ICC 0.93 to 0.94). Cough sound measurement has the advantage of being non-invasive and suitable for ambulatory monitoring and further studies should now assess its responsiveness as a measure of cough intensity.
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Kastelik, Jack A. "Investigation and assessment of chronic cough." Thesis, University of Hull, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402480.
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Kelly, Helana Ellen. "The effect of titrated fentanyl on cough response in healthy participants." Thesis, University of Canterbury. Department of Communication Disorders, 2014. http://hdl.handle.net/10092/9158.
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Background: One population prone to aspiration pneumonia and impaired cough is the postoperative patient. Postoperative pneumonia is the third most common complication among surgical patients after urinary tract and wound infections (Wren, Martin, Yoon, & Bech, 2010). A patient who has their surgical course complicated by aspiration pneumonia has increased morbidity, increased length of hospital stay and places greater demands on the health system. Mortality rates are cited as high as 70% (Wren, et al., 2010). Despite the prevalence of postoperative pneumonia and the high morbidity and mortality rates, little is known about the effect of anaesthesia on swallowing and airway protection. This study investigated the effect of clinical doses of fentanyl on suppressed cough reflex in healthy participants.
Materials and Methods: After receiving ethical approval, 14 young, healthy participants gave informed written consent and completed the study protocol. Each participant received a total of 2 mcg/kg of fentanyl in four doses administered at five-minute intervals. Fentanyl effect site concentrations (ESC) were estimated using a standard pharmacokinetic model. During the administration period, suppressed cough response testing (SCR) with nebulised citric acid was performed after each fentanyl dose. Citric acid was presented in increments of 0.2M from each participant’s baseline cough response until a present-strong response was achieved. During the post-administration period, SCR was compared with reducing effect site concentrations to determine the time course for resolution of cough suppression.
Results: Suppressed cough threshold increased and decreased in parallel with modeled fentanyl effect site concentrations. Mean citric acid concentration increased from 0.5M at baseline to 0.6M after 0.5 mcg/kg of fentanyl, 0.7 M after 1 mcg/kg of fentanyl, 0.9M after 1.5 mcg/kg of fentanyl and 1.2M after 2 mcg/kg of fentanyl. Predicted effect site concentrations after final doses of fentanyl (2 mcg/kg) were 1.89 ng/mL (1.81-1.96), well within the range seen clinically in the postoperative period. After the final dose of fentanyl, participants had on average 3.4 increments of change in their cough response (at increments of 0.2M).
Conclusion: SCR testing with citric acid is sensitive enough to mirror changes in fentanyl ESC in healthy, young participants. The degree of reflex suppression seen has been associated with an 8-fold increase in aspiration risk in the general medical patient with dysphagia (Miles, Moore, McFarlane, Lee, Allen, Huckabee, 2013). Further research into the application of SCR in the postoperative period may help clinical decisions regarding safety to commence oral intake.
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Haji, Sadeghi Mahboobeh. "The emerging role of the eosinophil and its measurement in chronic cough : airway inflammation in chronic cough." Thesis, University of Hull, 2017. http://hydra.hull.ac.uk/resources/hull:16543.
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Although the aetiology of chronic cough in guidelines is clearly stated as asthma and related syndromes, gastro-oesophageal reflux disease, and upper airways disease, the inflammatory mechanisms underlying these conditions differ. Recent studies on asthma have increasingly focused on its molecular phenotypes instead of clinical characteristics. Predominantly in this thesis I hypothesize that by dividing cough patients into the clinical characteristics of eosinophilic and neutrophilic groups will enhance our ability to recognise the type of airway inflammation, and consequently will lead us to more targeted treatment approaches. To investigate this hypothesis I conducted a randomized, single centre, open label, controlled, clinical trial to examine the outcome of anti-inflammatory therapy with either montelukast or prednisolone in 50 patients with chronic cough. Furthermore, I studied the epidemiology of 137 chronic cough patients attending the Hull cough clinic. Results from the clinical study demonstrated that patients with FeNO≤20ppb had twice the number of coughs compared with patients with FeNO≥30ppb. This was reflected on quality of life as assessed by the LCQ and HARQ. Confirming this finding I found in the epidemiological study, that patients attending the hull cough clinic with FeNO≤25ppb scored significantly higher in HARQ compared with FeNO≥25ppb. In the clinical trial study I have shown that FeNO was a good marker for eosinophilic inflammation. There was a high degree of correlation with FeNO, blood and sputum eosinophilia thus confirming phenotypic identity. Whether the FeNO can be used to identify the different characteristics between eosinophilic and non-eosinophilic coughs needs further investigation. Cough patients in both low and high FeNO groups have shown a similar response to montelukast despite anticipating little or no effect in those without eosinophilic inflammation. These results suggest that response to montelukast may not be predicted by presence of eosinophilic biomarkers alone but may be act by effecting localised leukotriene mediated inflammation.
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Torvaldsen, Siranda. "The epidemiology and prevention of pertussis in Australia." Thesis, The University of Sydney, 2001. http://hdl.handle.net/2123/808.
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Pertussis (whooping cough) remains an important public health problem in Australia. Although mortality and morbidity from pertussis declined dramatically following the introduction of mass vaccination programs in 1953, the level of morbidity remains unacceptably high for a vaccine-preventable disease. Aims and methods The primary aims of this thesis were (i) to ascertain the epidemiology of pertussis in Australia between 1993 and 2000 by analysing and interpreting sources of routinely collected data on pertussis; and (ii) to examine the effectiveness of vaccination against pertussis in a number of ways. Data from three primary national sources (notifications of disease, hospitalisations for pertussis and death certificates) were used to examine the burden from pertussis in Australia over these eight years. Analyses included the age distribution of cases, temporal and geographic trends, comparisons of notification and hospitalisation data, and the impact of differences in the method of diagnosis of notified cases between years and age groups. In addition to analyses at the national level using data from the national databases, further detailed analyses were undertaken at the State level for New South Wales (NSW), the most populous Australian State. Pertussis vaccine coverage was estimated using data from the recently established Australian Childhood Immunisation Register (ACIR); these data were also used to track the transition from whole-cell to acellular pertussis vaccines. The different types of studies used to evaluate vaccine effectiveness were reviewed, and a method suitable for ongoing estimation of vaccine effectiveness in Australia was developed. This was then applied to the NSW data, to determine the effectiveness of pertussis vaccination in this State. Main findings The annual notification rate for pertussis in Australia ranged from 23–59 per 100 000 population over the eight years. Infants had the highest notification and hospitalisation rates in Australia — they accounted for 5 percent of notifications, 61 percent of hospitalisations and 100 percent of deaths. Age-specific notification and hospitalisation rates in children aged less than two years strongly suggested a protective effect of vaccination, with the greatest reduction in rate coinciding with eligibility to receive a second dose of pertussis vaccine at four months of age. Notification rates among 5–9 year olds progressively decreased in successive age cohorts, consistent with an effect of the introduction in 1994 of a pertussis vaccine booster for preschool-aged children. Although adults (persons aged 15 years or more) accounted for half the notifications, they had the lowest notification rate. The highest numbers of pertussis notifications were in 1997, when most jurisdictions experienced an epidemic. Notification and hospitalisation rates varied across the States and Territories and also across smaller geographic regions in NSW. Areas and years with high notification rates tended to also have high hospitalisation rates, suggesting that trends in notifications reflected trends in incidence. The number of infant hospitalisations in NSW between July 1993 and June 1999 exceeded the number of notifications by 32 percent, highlighting the extent of under-notification. Overall, and particularly amongst those aged more than 12 months, the majority of cases notified in NSW were based on the results of serological tests. The proportion diagnosed by culture of the organism was greatest in infants; the proportion diagnosed by serological tests increased with age. There was no evidence that the use of serology had increased since 1994 in NSW, hence changes in notification rates after this time are unlikely to be attributable to increased use of serological diagnosis. ACIR records indicated that in December 2000, 92 percent of one-year-old children had received three doses of diphtheria-tetanus-pertussis (DTP) vaccine and 90 percent of two-year-olds had received four doses. Vaccine coverage varied by jurisdiction. Since 1997, there was an increased use of DTP vaccines containing acellular pertussis components with a corresponding decrease in the use of vaccines containing whole-cell components. In 2000, almost all DTP vaccines administered contained acellular pertussis components. The results of the vaccine effectiveness study showed that pertussis vaccination was highly effective at preventing pertussis in NSW children, as measured by notified cases. Vaccine effectiveness was highest (91 percent) in the youngest age group ((8–23 months) and lowest (78percent) in the oldest age group (9–13 years). The screening method has not previously been used to estimate pertussis vaccine effectiveness in Australia. Conclusions This thesis demonstrates the value of integrating varied data sources in estimating the disease burden from pertussis. The data presented here show that the disease burden is substantial in all age groups, despite high levels of vaccine coverage in infants and children. This problem of disease control does not appear to be due to lack of vaccine effectiveness, but there is evidence of waning immunity over time. The analyses presented here form a basis for the ongoing monitoring of trends in pertussis epidemiology following the replacement of whole-cell by acellular pertussis vaccines, and will assist consideration of the need for additional booster doses in adolescents and adults.
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Torvaldsen, Siranda. "The epidemiology and prevention of pertussis in Australia." University of Sydney. Paediatrics and Child Health, 2001. http://hdl.handle.net/2123/808.
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Pertussis (whooping cough) remains an important public health problem in Australia. Although mortality and morbidity from pertussis declined dramatically following the introduction of mass vaccination programs in 1953, the level of morbidity remains unacceptably high for a vaccine-preventable disease. Aims and methods The primary aims of this thesis were (i) to ascertain the epidemiology of pertussis in Australia between 1993 and 2000 by analysing and interpreting sources of routinely collected data on pertussis; and (ii) to examine the effectiveness of vaccination against pertussis in a number of ways. Data from three primary national sources (notifications of disease, hospitalisations for pertussis and death certificates) were used to examine the burden from pertussis in Australia over these eight years. Analyses included the age distribution of cases, temporal and geographic trends, comparisons of notification and hospitalisation data, and the impact of differences in the method of diagnosis of notified cases between years and age groups. In addition to analyses at the national level using data from the national databases, further detailed analyses were undertaken at the State level for New South Wales (NSW), the most populous Australian State. Pertussis vaccine coverage was estimated using data from the recently established Australian Childhood Immunisation Register (ACIR); these data were also used to track the transition from whole-cell to acellular pertussis vaccines. The different types of studies used to evaluate vaccine effectiveness were reviewed, and a method suitable for ongoing estimation of vaccine effectiveness in Australia was developed. This was then applied to the NSW data, to determine the effectiveness of pertussis vaccination in this State. Main findings The annual notification rate for pertussis in Australia ranged from 23�59 per 100 000 population over the eight years. Infants had the highest notification and hospitalisation rates in Australia � they accounted for 5percent of notifications, 61percent of hospitalisations and 100percent of deaths. Age-specific notification and hospitalisation rates in children aged less than two years strongly suggested a protective effect of vaccination, with the greatest reduction in rate coinciding with eligibility to receive a second dose of pertussis vaccine at four months of age. Notification rates among 5�9 year olds progressively decreased in successive age cohorts, consistent with an effect of the introduction in 1994 of a pertussis vaccine booster for preschool-aged children. Although adults (persons aged 15 years or more) accounted for half the notifications, they had the lowest notification rate. The highest numbers of pertussis notifications were in 1997, when most jurisdictions experienced an epidemic. Notification and hospitalisation rates varied across the States and Territories and also across smaller geographic regions in NSW. Areas and years with high notification rates tended to also have high hospitalisation rates, suggesting that trends in notifications reflected trends in incidence. The number of infant hospitalisations in NSW between July 1993 and June 1999 exceeded the number of notifications by 32percent, highlighting the extent of under-notification. Overall, and particularly amongst those aged more than 12 months, the majority of cases notified in NSW were based on the results of serological tests. The proportion diagnosed by culture of the organism was greatest in infants; the proportion diagnosed by serological tests increased with age. There was no evidence that the use of serology had increased since 1994 in NSW, hence changes in notification rates after this time are unlikely to be attributable to increased use of serological diagnosis. ACIR records indicated that in December 2000, 92percent of one-year-old children had received three doses of diphtheria-tetanus-pertussis (DTP) vaccine and 90percent of two-year-olds had received four doses. Vaccine coverage varied by jurisdiction. Since 1997, there was an increased use of DTP vaccines containing acellular pertussis components with a corresponding decrease in the use of vaccines containing whole-cell components. In 2000, almost all DTP vaccines administered contained acellular pertussis components. The results of the vaccine effectiveness study showed that pertussis vaccination was highly effective at preventing pertussis in NSW children, as measured by notified cases. Vaccine effectiveness was highest (91percent) in the youngest age group (8�23 months) and lowest (78percent) in the oldest age group (9�13 years). The screening method has not previously been used to estimate pertussis vaccine effectiveness in Australia. Conclusions This thesis demonstrates the value of integrating varied data sources in estimating the disease burden from pertussis. The data presented here show that the disease burden is substantial in all age groups, despite high levels of vaccine coverage in infants and children. This problem of disease control does not appear to be due to lack of vaccine effectiveness, but there is evidence of waning immunity over time. The analyses presented here form a basis for the ongoing monitoring of trends in pertussis epidemiology following the replacement of whole-cell by acellular pertussis vaccines, and will assist consideration of the need for additional booster doses in adolescents and adults.
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Birring, Surinder S. "Clinical and laboratory features of chronic cough." Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/10329.
Full textAbstract:
Chronic cough is a common presenting symptom to both general practice and respiratory clinics and in up to 20% of patients, the cough remains unexplained after extensive investigation and treatment trials. In this thesis, we have shown that patients with idiopathic chronic cough are predominantly female, have an onset of cough in middle age and have a high prevalence of organ specific autoimmune disease, particularly hypothyroidism. We found that idiopathic chronic cough is associated with a bronchoalveolar lavage lymphocytosis and have suggested that this is due to homing of activated lymphocytes from the primary site of autoimmune inflammation to embryologically related structures such as the airways, analogous to the mechanism thought to be responsible for airway complications of inflammatory bowel disease. The concept that chronic inflammation of foregut structures can be associated with airway symptoms, inflammation and damage is also supported by our finding of a striking excess of cases of treated hypothyroidism amongst a predominantly elderly non-smoking female population with fixed airflow obstruction and a 2-3 fold excess of respiratory symptoms in a cohort of patients with autoimmune hypothyroidism and another with inflammatory bowel disease. We have also shown raised histamine concentrations in airway secretions of patients with idiopathic chronic cough, which suggests a possible mechanism whereby airway inflammation results in cough and raises the possibility that antihistamines may have a therapeutic role in idiopathic chronic cough. Finally, recognising the major impact of chronic cough on health status and the paucity of objective measures available for the assessment of cough, we developed the Leicester Cough Questionnaire, which is a 19-item cough specific quality of life questionnaire.
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Hutchinson, Nicola-Xan. "Studies of cough in Idiopathic Pulmonary Fibrosis." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/94471/.
Full textAbstract:
A dry cough is a common symptom described in patients with IPF and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however there is evidence that altered cough neurophysiology and sensitisation plays a roleY IPF patients have an enhanced cough reflex sensitivity to the inhalation of capsaicin. It was hypothesised that IPF patients have increased airway expression of the capsaicin receptor TRPVF1 and a coFexpressed receptor TRPAF1. Bronchial biopsies were obtained in 16 IPF patients, 11 chronic cough patients and 8 controls. Quantitative PCR was used to detect TRPVF1 and TRPAF1 gene expression, with immunohistochemistry demonstrating protein expression. Mean TRPVF1 and TRPAF1 gene expression was higher in IPF patients compared with controls, but the difference did not reach statistical significance. Immunostaining supported these findings. Gastroesophageal reflux is common in IPF patients and has also been implicated. An inFvitro study using cultured pulmonary epithelial cells was conducted to assess the expression of these receptors in a cell model of gastric reflux. TRPVF1 and TRPAF1 gene expression was demonstrated in pulmonary epithelial cells of bronchial and alveolar origin. No significant difference in receptor expression level was seen in either cell line when exposed to the major constituents of gastric refluxate. This study suggests that a structural upFregulation of central airway TRP receptors is not the key mechanism for cough in IPF patients. Similarly, it does not support the role of the individual constituents of gastric refluxate resulting in cough hypersensitivity through a physical upFregulation of receptors in pulmonary epithelial cells. Overall this thesis outlines the complexity of the cough reflex. It is probable that cough in IPF results from the cumulative manifestation of various physiological changes and mechanisms.
20
Toop, Leslie John. "Cough sound analysis in children with asthma." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361104.
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Aleixo, de Matos SeÌrgio Guilherme. "Automatic detection and analysis of cough sounds." Thesis, University of Leicester, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437913.
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Iwata, Toshiyuki. "Mechanical stimulation by postnasal drip evokes cough." Kyoto University, 2016. http://hdl.handle.net/2433/215415.
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Rafiq, Muhammad. "Mechanically assisted cough in motor neurone disease." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/6875/.
Full textAbstract:
Motor Neurone Disease (MND) is a disabling and inevitably fatal disease, usually with a life expectancy of 2-3 years from symptom onset. It is characterised by progressive wasting and weakness in bulbar, limb and respiratory muscles. There is no cure and treatment is mainly symptomatic. Neuromuscular respiratory failure, with or without a chest infection, is the commonest cause of death in MND patients. It has been shown that supporting respiratory function with non-invasive ventilation, improves survival and quality of life despite progression of the disease. The patients with respiratory muscle weakness may also have a weak cough and significant difficulty in clearing their airways of respiratory secretions. This causes much discomfort, predisposes to chest infections and adversely affects quality of life. Due to lack of evidence in this area, there is no clear consensus or guideline about how best to help such patients. This work aimed to establish the role of cough augmentation techniques in MND. A total of 40 eligible patients with MND were randomised to the breath-stacking technique (n=21) or Mechanical Insufflator-Exsufflator MI-E (n=19) and followed-up at 3 monthly intervals for at least 12 months or until death. All patients were diagnosed with respiratory failure and offered non-invasive ventilation (NIV). The primary outcome measure was the number of days with symptoms of chest infection, treated with antibiotics, in the community or in hospital. Survival and quality of life benefit, assessed by short form 36 mental component summary (MCS) and sleep apnoea quality of life index symptoms domain (sym), were the secondary outcome measures. There were 13 episodes of chest infection in the breath-stacking group and 19 episodes in MI-E group (p=0.87), requiring 90 and 95 days of antibiotics respectively (p=0.85). There were 6 episodes of hospitalisation in each group (p=0.87). The mean duration of symptoms per chest infection was 6.9 days in the breath-stacking group and 3.9 days in MI-E group (p=0.16). The chance of hospitalization, in the event of a chest infection was 0.46 in the breath-stacking group and 0.31 in MI-E group (p=0.47). Median survival in the breath-stacking group was 535 days and 266 days in the MI-E group. The MCS score was maintained above 75% of baseline for a median of 329 days in the breath-stacking group and 205 days in MI-E group (p=0.41). A non-significant improvement in quality of life, compared to baseline was observed in both interventional groups. In MND patients with respiratory failure, cough augmentation is likely to help maintain quality of life in the presence of the distressing symptom of weakened ability to cough. This study was not powered to assess the potential impact on life expectancy. There was no significant difference in terms of pulmonary morbidity between the two groups. A trend towards fewer chest infections was observed in the breath-stacking group, and a trend for reduced duration of antibiotic use and decreased chance of hospitalization in the event of a chest infection was observed in the MI-E group, though these changes did not reach statistical significance. These results are insufficient to draw firm conclusions, but support routine domiciliary use of a suitable cough augmentation technique in patients with ALS requiring respiratory support. The breath-stacking technique may be prescribed for domiciliary use with the onset of respiratory failure. MI-E may be useful in the event of a chest infection when it has the potential to reduce the duration of antibiotic use and chance of hospitalisation or when breath-stacking is no longer sufficient to maintain patient comfort. The results of this trial provide data useful for the power calculations required for a larger-scale multi-centre randomised trial.
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Monroe, Margaret Delia. "Citric acid inhalation cough challenge: Establishing normative data." Thesis, University of Canterbury. Communication Disorders, 2010. http://hdl.handle.net/10092/4149.
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One of the most elusive challenges in the diagnosis and treatment of dysphagia is the
reliable identification of silent aspiration (aspiration in the absence of cough). The citric acid
inhalation cough challenge offers potential for aiding in identification of silent aspiration;
however clinical application of this technique is currently problematic due to an absence of
normative data. Therefore, this study aimed to establish a normative data set for the Citric-
Acid Inhalation Cough Challenge, as administered with facemask method. 80 healthy
subjects will participate in this study, constituting 2 age groups: above and below 60 years,
with equal gender representation. On 3 separate trials, they will be asked to passively inhale,
via a facemask, nebulised citric acid of concentrations ranging from 08M to 2.6M with
placebo interspersed. ‘Natural cough thresholds’ (NCT) and ‘Suppressed Cough Thresholds’
(SCT) will be reached when subjects cough on at least 2 out of 3 trials. The majority (92.5%)
of participants reached Natural Cough Threshold by 0.8M, with 68% demonstrating
Suppressed Cough Threshold also at this concentration. There were no significant
differences found between males and females (p<0.05) for either NCT (p=0.9885) or SCT
(p=0.44). Whilst no difference was found between youngers and elders for NCT (p=0.7254),
there was a significant difference for SCT (p=0.018), with youngers better able to suppress
cough. Over 90% of healthy people were found to elicit cough at 0.8M, inferring that this
level would be an adequate guide for use by clinicians testing for presence/absence of cough.
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Piyawong, Wirawan. "Spatio-temporal numerical modelling of whooping cough dynamics." Thesis, Brunel University, 2001. http://bura.brunel.ac.uk/handle/2438/6626.
Full textAbstract:
The SIR (Susceptible/Infectious/Recovered) whooping cough model involving nonlinear ordinary differential equations is studied and extended to incorporate (i) diffusion (ii) convection and (iii) diffusion-convection in one-space dimension. Firstand second-order finite-difference methods are developed to obtained the numerical solutions of the ordinary differential equations. Though implicit in nature, with the resulting improvements in stability, the methods are applied explicitly. The proposed methods are economical and reliable in comparison to classical numerical methods. When extended to the numerical solutions of the partial differential equations, the solutions are found by solving a system of linear algebraic equations at each time step, as opposed to solving a non-linear system, which often happens when solving non-linear partial differential equations.
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McFarlane, Mary. "A Pilot Study of Change in Laryngeal Cough Threshold Sensitivity and PAS(Penetration Aspiration Scale) Score Within the Acute Stage." Thesis, University of Canterbury. Speech and language science, 2013. http://hdl.handle.net/10092/10734.
Full textAbstract:
Background: Cough Reflex Testing (CRT) has been shown to be useful in the challenging task of
identifying silent aspiration (aspiration without a cough response). With the emergence of the routine
clinical use of CRT in the acute stroke population, the following clinical conundrum often arises:
Does passing a previously failed CRT mean the risk of silent aspiration has resolved? The purpose of
this study was to evaluate the association between change in laryngeal cough threshold sensitivity and
change in PAS (Penetration Aspiration Scale) score within the acute stage post-stroke. Methods: This was a prospective longitudinal pilot study of 20 acute stroke patients utilizing a
Cough Reflex Threshold Test (CRTT) at 0.4M, 0.6M and 0.8M citric acid concentrations and
Fiberoptic Endoscopic Evaluation of Swallowing (FEES). A cough response threshold was obtained
from the CRTT and a PAS (penetration aspiration scale) score from FEES. Inclusion criteria required
a PAS score of 4 or above on preliminary FEES or impaired CRT threshold as defined by weak or
failed cough test result at 0.8M citric acid concentration. Both test methods were repeated every four
days for 20 days or until the participant no longer aspirated/penetrated and had a normal result on
CRTT on two consecutive assessment sessions. Agreement between changes in the two tests was
evaluated using the Cohen’s Kappa statistic.
Results: Eighteen of the twenty participants in this study aspirated on initial assessment, ten of which
were silent. One participant continued to aspirate at study completion. On initial assessment eleven
participants had a C2 response threshold at 0.4M citric acid concentration and three participants failed
to reach threshold at 0.8M citric acid concentration. At study completion, 18 participants had a C2
response threshold at 0.4M citric acid concentration and one participant failed to reach threshold at
0.8M citric acid concentration. During the study, sixty-six re-assessments took place; there were
fifteen incidences of improved cough response threshold on re-assessment and thirty-one incidences
of improved PAS score. There was no significant agreement between improved laryngeal cough reflex threshold and improved PAS score during the acute stage Kappa = 0.0598 (p <.0.574), 95% CI (-
0.1496- 0.2692).
Conclusion: Significant limitations of this study included small data set and potential flooring effect
of the CRT. Due to the limitations of this study, no conclusions can be made as to the appropriateness
of reinstating oral intake based on passing a previously failed CRT.
27
Cheung, Yung-yan Terence. "Whooping cough : are we seeing the reemergence of the infection in Hong Kong? /." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/b39724049.
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Venkatesan, Priya. "Modulation of airway neural control and the cough reflex." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326081.
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Polley, L. "The role of novel Ion Gates channels in cough." Thesis, Queen's University Belfast, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517507.
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Johnston, I. D. A. "The current severity and longterm sequelae of whooping cough." Thesis, University of Cambridge, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605661.
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Fowles, Helen Elizabeth. "An investigation into the mechanism of inhalational cough challenge." Thesis, University of Hull, 2018. http://hydra.hull.ac.uk/resources/hull:16542.
Full textAbstract:
Chronic cough is a common problem. Historically treatments have focussed on treating underlying physiological causes. More recently an overarching theory of cough hypersensitivity syndrome has developed. In-vitro models of cough have not successfully translated into human studies. Testing the cough reflex in humans via inhalational cough challenge has been utilised since the 1950s. The mechanisms of cough challenge are poorly understood. This thesis sets out to investigate these mechanisms further in three different experiments. By altering pH in a citric acid challenge and measuring cough response, I show that cough hypersensitivity is not due purely to a shift in the dose response curve to pH, but also an alteration in the pattern of response to a given stimulus. Designing a cough challenge with a novel agent (ATP) revealed that the cough response to ATP is clearly delineated from that of AMP. The response to ATP in chronic cough is heightened, but not to such a degree as to implicate the acute response to inhalation of ATP in the pathophysiology of cough hypersensitivity syndrome. Comparing four cough challenges – the commonly used citric acid and capsaicin; the slightly less utilised distilled water fog challenge; and the new ATP challenge – proved that all challenges show less intra-patient reproducibility in chronic cough patients. Inhaled ATP cough challenge responses correlated with citric acid and capsaicin challenge suggesting overlap in mode of action. All experiments explore the cough challenge further in a group who have had little previous cough challenge investigation: the patient with chronic cough. They reveal that patients with cough hypersensitivity syndrome have not only a heightened but an unpredictable cough reflex, and that this is not due solely to upregulation of the cough receptors at peripheral nerve endings. Inhalational cough challenge plays an important role in further elucidating the mechanisms of chronic cough.
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Harle, Amelie. "The characterisation and treatment of cough in lung cancer." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/the-characterisation-and-treatment-of-cough-in-lung-cancer(f0ba551d-c7c8-4b5c-8d56-9b0c32d6d3ab).html.
Full textAbstract:
Cough in lung cancer (LC) is a significant unmet need. There are no evidence-based effective antitussives for its treatment and a lack of well-designed trials incorporating validated cough assessment tools and placebo controls. There is little research on its underlying mechanisms, perhaps with the assumption that it is simply 'due to the cancer'. Therefore, we have sought to characterise cough in terms of its severity, impact on quality of life, frequency and prevalence using LC specific subjective and objective assessment tools for the first time. We have also explored its potential mechanisms and treatment. Published preclinical data show that the substance P/neurokinin-1(NK1) pathway is implicated in cough in 5 different species. This pathway is targeted by the antiemetic aprepitant in humans. Data on the use of aprepitant as a novel antitussive are presented. To characterise cough and assess cough assessment tools in a cohort of patients with LC attending outpatient clinics, subjective and objective cough assessment tools including 24-hour ambulatory cough monitoring (ACM), were used to determine the cough severity, frequency, impact and cough- associated clinical factors in a longitudinal study. To determine cough prevalence, a cross sectional study of all patients attending thoracic oncology outpatient clinics in a single centre over a defined period were approached to determine whether they had a cough, to provide demographic and cancer related data and if applicable, to complete the Manchester Cough in Lung Cancer Scale (MCLCS) cough impact questionnaire and the cough severity visual analogue scale. To explore the role of the NK1 pathway in cough in patients with LC, a single-arm randomised placebo controlled pilot trial assessing aprepitant for the treatment of cough was conducted. The presented data demonstrated that cough affects over half of patients with LC, representing a huge unmet clinical need. Over 2/3rds of patients felt that their cough was severe enough to warrant treatment and over 1/4 described it as painful. Patients with LC suffer from a very severe and frequent cough. Its impact is considerable, with effects on physical, psychological and social domains. The longitudinal study is the first to report that cough severity and impact is predicted by gastro-intestinal co-morbidities rather than cancer related factors. The presented data demonstrate that ACM is feasible and acceptable to patients with LC. This provides researchers with an objective endpoint for use in clinical trials. The MCLCS performs well and is valid. The cough intervention trial is the first to demonstrate that aprepitant is associated with lower subjective cough scores and cough frequency using validated cough assessment tools. No antitussive therapy study has ever shown a positive antitussive effect using both types of cough assessment tools in the LC population. This suggests that the substance P/NK1 pathway is implicated in cough in LC and identifies this as a potential new therapeutic target, providing exciting data and hope for future patients with LC.
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Maher, Ann. "Identification of the prostanoid receptor mediating PGE2-induced cough." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/5490.
Full textAbstract:
Prostaglandin E2 (PGE2) may provide a novel therapy for the treatment of inflammatory airway diseases as it has been shown to confer both bronchodilator and anti-inflammatory activity in asthmatic subjects. However, PGE2 can cause irritancy of the upper airway resulting in a reflex cough. The aim of this thesis was to identify which of the 9 prostanoid receptors (EP1, EP2, EP3, EP4, DP, FP, IP, TP and CRTh2) mediate the PGE2-induced cough. The cough reflex is under the control of sensory afferent nerve fibres that innervate the lungs via the vagus nerve. Using an in vitro model of vagal sensory nerve depolarisation, gene and protein expression techniques and a guinea-pig cough system, I investigated the prostanoid receptor(s) responsible for the PGE2-induced depolarisation of the vagus nerve and cough. A conscious guinea-pig cough system was characterised and I confirmed that guinea-pigs, like humans, cough in response to PGE2. Isolated vagus nerves from guinea-pig, mouse and human were characterised in response to PGE2 and other tussive stimuli, capsaicin and low pH. Isolated nerves from these species behave similarly suggesting that effects observed in these small animals translate to man. It was discovered that depolarisation to PGE2 was virtually abolished in isolated vagus nerves from EP3 receptor knockout (KO) mice. This suggests that the response to PGE2 is mediated by the EP3 receptor, supported by evidence that an EP3 receptor antagonist (L826266) inhibited the response to PGE2 in isolated vagus nerves from guinea-pig, mouse and human. Expression of the EP3 receptor was confirmed in guinea-pig vagal nerve ganglia (containing the cell bodies of nerves carried in the vagus) using Taqman RT-PCR and immunohistochemical staining. Ultimately, I demonstrated the role of the EP3 receptor in vivo using a selective EP3 receptor antagonist to attenuate PGE2-induced cough. This thesis identifies the receptor responsible for PGE2-induced cough representing a key step in developing a drug that is anti-inflammatory and a bronchodilator but devoid of tussive side effects
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Nasra, Julie. "Modulation of Sensory Nerve Function and the Cough Reflex." Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/4252.
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Cough is an important protective reflex. Sensory nerve activity mediating cough may be enhanced during disease. Current antitussives possess little clinical efficacy, therefore research is needed to investigate the modulation of airway sensory nerves in order to understand the mechanisms driving chronic cough. A conscious guinea-pig cough model using different tussive stimuli, known to elicit cough in man, was established. Corresponding in vitro effects of these tussive agents on sensory nerve activation were characterised. These agents were also characterised into sub-types as they produced distinct patterns of response. Cigarette smoke (CS) exposure elicited distinct effects on the cough reflex in conscious guinea-pigs and on sensory nerve activity measured in vitro; CS enhanced responses to citric acid (CA), capsaicin (CAPS) and bradykinin, inhibited a prostaglandin E2 (PGE2)-induced response and had no effect on the response to hypertonic saline. The CS model demonstrated neutrophilia and increased mucus in the airways. Focussing on mechanisms driving enhanced cough, revealed that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), may play a role in cough reflex sensitisation. An in vitro bioassay confirmed that NGF and BDNF exhibited bioactivity and the anticipated species cross-reactivity. CS exposure augmented the expression of transient receptor potential vanilloid 1 (TRPV1) in vagal sensory nerve ganglion. Pharmacological modulation of guinea-pig and human vagus nerve activation showed that TRPV1 antagonists, capsazepine and SB366791, abolished CAPS-induced depolarisation, partially inhibited low pH, bradykinin and PGE2-induced responses and had no effect on hypertonic saline. Despite positive in vitro and pharmacokinetic analyses, TRPV1 antagonists did not inhibit CAPS-induced cough in vivo. Further work is required to expand upon these findings. This thesis contains an assessment of the effects of sensory nerve modulation in guinea-pig models of cough. Understanding the neural mechanisms associated with this research may help to guide the development of novel antitussive therapies.
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Srikannathasan, Velupillai. "Biochemical and structural analysis of Bordetella pertussis lipopolysaccharide A biosynthetic pathway enzymes." Thesis, University of East Anglia, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273576.
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Al-Fellah, Giamal Nouri. "Inactivation of Bordetella pertussis by rat lung lavage fluids (LLF)." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263427.
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Brotherston, Christopher. "Interaction of Bordetella pertussis adenylate cyclase toxin with target cells." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263429.
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MacDonald-Fyall, Julia. "The protective and immunomodulatory properties of Bordetella pertussis adenylate cyclase toxin." Thesis, University of Glasgow, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248267.
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Garrod, Tracey. "Partial purification and characterisation of Bordetella bronchiseptica dermonecrotic toxin." Thesis, University of Reading, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239514.
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Funnell, Simon Gordon Paul. "Mechanisms of colonisation of mammalian tissues by Bordetella pertussis." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239726.
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Choudry, Nozhat Bano. "Investigation of the sensitivity of the cough reflex in humans." Thesis, Imperial College London, 1991. http://hdl.handle.net/10044/1/46713.
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Decalmer, Samantha Clare. "Phenotyping patients with chronic cough presenting to a specialist clinic." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494302.
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Introduction: Chronic cough is a common complaint, accounting for one third of all referrals to chest physicians. National and international guidelines exist for treatment and investigation, despite this, in upto 42% of patients, no cause for cough is found. Whether this represents undiagnosed pathology, inadequate treatment or 'idiopathic cough' is unclear. Gastro-oesophageal reflux is reported as a common cause of chronic cough but the exact mechanism by which this occurs is unclear. Both direct cough receptor stimulation (microaspiration and LPR), and indirect stimulation (an oesophago-tracheo-bronchial reflex) have been proposed. Methods: 100 chronic cough patients have been comprehensively investigated, incorporating routine bronchoscopy and oesophageal impedance/pH into the diagnostic algorithm. Cough has been evaluated, both before and after treatment, by subjective assessment and objective cough sound monitoring. Results: Subjective assessment of cough was found to be affected by patient anxiety and depression and related only moderately to cough frequency.
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Turner, Richard. "A description of cough in tuberculosis and other respiratory conditions." Thesis, Queen Mary, University of London, 2016. http://qmro.qmul.ac.uk/xmlui/handle/123456789/23613.
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Cough is common but has been under-researched. In tuberculosis cough is probably of particular relevance in transmitting infection. This thesis explores several interlinking areas. Regarding how best to measure cough, coughs are shown to be recognizable to the human ear, but automated cough monitors can disagree with auditory cough counting. A novel approach to testing cough reflex sensitivity is described, E62.5. There was no evidence to support the hypothesis that cough has unique characteristics in tuberculosis, in terms of symptoms, frequency and clustering. A significant reduction of cough frequency in tuberculosis is demonstrated overnight. Clinical correlates of 24hour cough frequency were explored; female sex in unexplained chronic cough, and sputum smear status in tuberculosis were important, and possibly transfer factor in pulmonary fibrosis and duration of symptoms prior to treatment in COPD exacerbations. Cough frequency correlated poorly with symptoms. There seem to be both generic and disease-specific mechanisms associated with cough. This was further suggested by a faster reduction in cough frequency with treatment in pneumonia than in acute asthma and COPD exacerbations, correlating with C-reactive protein decline only in pneumonia. A serial reduction in 24-hour cough frequency in tuberculosis during the whole course of treatment was demonstrated, a potentially novel approach to measuring treatment response. The role of genetic polymorphism in the cough receptor gene TRPV1 was explored, but, at least in chronic cough was not demonstrated to predict coughing. Regarding the infectiousness of coughs, an airborne particle counter was shown not to be sensitive enough for measuring droplets released during coughing in room air. However, I demonstrate for the first time a significant association between 24-hour cough frequency in TB and household infection. This work has set a foundation for the further investigation of the mechanisms, processes and patterns of coughing with respect to tuberculosis transmission and other contexts.
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Hilton, Emma. "Towards an understanding of the neurophysiology of cough in humans." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/towards-an-understanding-of-the-neurophysiology-of-cough-in-humans(f314ffdd-9ea0-4732-af27-afd7f34f9ffa).html.
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Rationale: Chronic cough (cough >8 weeks) is common, leads to an impaired quality of life, and is difficult to treat. Despite intensive investigation, ~40% of patients referred to a specialist cough clinic will remain resistant to treatment targeted at peripheral triggers such as reflux disease, rhino-sinusitis or airways inflammation. An improved understanding of underlying mechanisms in such patients would facilitate drug development. I propose that there are several important similarities between pain and cough that can be exploited better to understand underlying mechanisms. In chronic pain, a long-lasting up-regulation of afferent pain processing may be generated by changes within the central nervous system, mediated by the NMDA receptor and/or by impaired inhibitory mechanisms. A similar central neuronal up-regulation of cough may also be responsible for the pathogenesis of chronic cough (CC). Methods: A series of experimental studies were performed to address this hypothesis. Firstly, the anti-tussive and analgesic effect of ketamine, an NMDA receptor antagonist, was investigated in CC patients and healthy controls (HC). Pain thresholds were measured using electrical stimulation in the oesophagus, pharynx and chest wall. Cough sensitivity was measured using standard capsaicin cough challenges. Secondly, I designed and tested novel capsaicin cough challenges in CC patients, asthmatics (A) and HC. ED50 (dose inducing and least 50% maximal cough frequency) and Cmax (maximal cough frequency) was compared by group and gender. Finally, I investigated 2 independent mechanisms of cough inhibition. Results:(i) CC patients, but not HC, had cough induced by oesophageal electrical stimulation, whilst pain thresholds were similar. Ketamine had a significant analgesic effect but no antitussive effect in CC or HC.(ii) CC patients had both cough hypersensitivity (lower ED50) and cough hyper-responsiveness (higher Cmax) on full capsaicin dose-response curves. (iii) Both a painful cold stimulus applied to the hand and conscious cough suppression significantly inhibited capsaicin-induced cough responses in CC and HC.Conclusions:CC patients exhibited increased oesophageal sensitivity to cough, but not pain, providing evidence for a process of central sensitisation in the brainstem. Higher capsaicin-induced cough frequencies in CC may also be mediated by an increased gain within the CNS, possibly because of failed tonic inhibitory mechanisms. Furthermore, CC patients may have poorer conscious control of coughing. In conclusion, an improved understanding of mechanisms in cough will provide a strong scientific rationale for the development of novel therapeutics.
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Advani, Abdolreza. "Epidemiological characterisation of Bordatella pertussis in Sweden, 1970-2004 /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-052-7/.
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Zawawi, Nor Shahrina. "Measuring voluntary cough and its relationship to the perception of voice." Thesis, University of Canterbury. Department of Communication Disorders, 2010. http://hdl.handle.net/10092/3923.
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Cough is a motor act of the laryngeal and respiratory systems. Features of coughing have been considered in the examination of respiratory, swallowing and voice disorders. Although some voice disorders have been linked to excessive coughing, the precise relationship between cough and voice remains unknown. The present study examined the acoustic features of cough across sex and age; and its relationship to the perception of voice production. A total of 30 cough samples and 30 voice samples were collected from 15 healthy females and 15 healthy males; ranging from young age (17-25 years old), middle-aged (30-45 years old) and older-age (60 years old & above). Coughs containing three distinct phases were submitted to an acoustic analysis of the long-term average spectrum (LTAS) and cough duration. Both cough and voice samples were examined perceptually by a group of 20 speech-language pathologists. Results found a distinct three-phase pattern of cough that was remarkably stable across sex and age. Significant differences were found in the duration of each phase of cough. Perception of cough was not significantly related to acoustic features of cough. Perceptual judgment of sex was comparable for both cough and voice samples. However, the accuracy of age recognition was higher for voice samples compared to cough samples. In addition, voice was judged to be healthier and stronger than cough. Overall, the results partially support the previous acoustic findings on cough. A strong relationship between the acoustics of cough and the perception of cough was not evident. Listeners judged voice differently from cough, except for sex recognition. The clinical implications of the findings are discussed.
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Gorringe, A. R. "The effects of growth conditions on the expression of virulence determinants of Bordetella pertussis." Thesis, University of Southampton, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235294.
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Berry, P. R. "Production of monoclonal antibodies to Bordetella pertussis as a means of identifying protective antigens." Thesis, University of Reading, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376819.
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Li, Jing-Li. "A molecular study of virulence factors of Bordetella species." Thesis, Open University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303193.
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A 1kb HinfI DNA fragment, containing a repeat DNA sequence element was isolated from a Bordetella pertussis BP348 cosmid gene bank. This repeat DNA sequence has subsequently been named IS148. The insertion sequence was demonstrated by have a high copy number only in B.pertissus and to be absent in Bordetella parapertussis and Bordetella bronchiseptica. Using a restriction fragment of IS148 labelled with radioactivity as a probe in DNA or whole cell dot blots between 10-100 cells could be detected or from 100pb-1ng DNA. Furthermore, a pair of oligonucleotide primers was synthesised corresponding to a central region of IS148 that could generate a 242bp fragment upon PCR amplification. The use of PCR amplification with specific primers allows the detection of 0.5pg of B.pertussis chromosomal DNA and as little as one B.pertussis cell. The prn genes encoding the outer membrane P.70 and P.68 pertactin from B.parapertussis and B.bronchiseptica have been cloned, sequenced and expressed in Escherichia coli. Analysis of the DNA sequences reveal that the genes have open reading frames capable of encoding proteins with molecular weights of 95,177 (P.95, B.parapertussis) and 93,996 (P.94, B.bronchiseptica). These precursors molecular are processed to form the P.70 and P.68 antigens on the surface of B.parapertussis and B.bronchiseptica respectively. Heterologous expression of the full-length gene encoding P.95 and P.94 in E.coli result in similar processing, with the P.70 and P.68 antigens targetted to the bacterial outer membrane. Comparison of P.95, P.94 and P.93, encoding homologous proteins from B.parapertussis, B.bronchiseptica and B.pertussis, shows a high degree (> 90%) of homology. The major differences between all three proteins occur in the number of repeat of the two families (Gly-Gly-Xaa-Xaa-Pro)n and (Pro-Gln-Pro)n of reiterated sequence motifs.
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Черняк, О. М., Г. С. Зайцева, О. Г. Васильєва, Олександр Іванович Сміян, Александр Иванович Смиян, Oleksandr Ivanovych Smiian, and О. В. Логвінова. "Особливості перебігу кашлюку в м. Суми та Сумській області." Thesis, Видавництво СумДУ, 2012. http://essuir.sumdu.edu.ua/handle/123456789/27426.
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