The present work confirmed that B. pertussis infection or pertussis toxin produce hypoglycaemia in mice. The hypoglycaemia was associated with hyperinsulinaemia, and both were abolished by destruction of the pancreatic β cells with alloxan. Impaired glucose counterregulatory mechanisms may also contribute to pertussis-induced hypoglycaemia, as the hypoglycaemic action of insulin was prolonged in pertussis infected mice. On the other hand, impaired responsiveness to lower doses of insulin was found. Pertussis-induced hyperinsulinaemia had two components. First, the increase in serum insulin in response to food intake was both greater and more prolonged in pertussis-infected mice. Second, infected or pertussis toxin-treated animals, unlike controls, showed a marked increase in serum insulin in response to certain stresses, such as ether, histamine, anoxia and 2-deoxyglucose. However, other stresses (LPS, cold and hypoxia) did not cause hyperinsulinaemia in pertussis infected mice. Stress-induced hyperinsulinaemia was also seen in normal mice receiving the a2- adrenoceptor blocking drug idazoxan. Stress-induced hyperinsulinaemia in a2 adrenoceptor blocked mice, but not in pertussis-treated mice, was prevented by β adrenoceptor blockade using propranolol. Adrenal demedullation or ganglionic blockade (using hexamethonium) in normal mice also allowed stress induced hyperinsulinaemia. Thus, adrenal medullary catecholamines may normally serve to prevent stress induced hyperinsulinaemia, which becomes unmasked when they are absent or when their action is prevented. Stress-induced hyperinsulinaemia in pertussis treated mice was unlikely to involve autonomic, cholinergic oropioid mechanisms as it was not blocked by hexamethonium, atropine or naloxone. Human infants with pertussis showed no hypoglycaemia compared with non-pertussis controls, although their plasma insulin concentrations were slightly but significantly raised. It remains possible that hyperinsulinaemia with resultant profound hypoglycaemia might occur in susceptible patients following exposure to pertussis-toxin (either during the disease or following vaccination).

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.

Rationale: The pathophysiologic differences between classic asthma (CA), cough variant asthma (CVA), and methacholine (MCh)-induced cough but normal airway sensitivity (COUGH) are poorly understood and may relate to differences in small airway function. We hypothesized that the bronchodilating and bronchoprotective effects of DIs are: (a) absent or impaired in individuals with CA; (b) impaired in individuals with CVA; and (c) preserved in those with COUGH. Purpose: To compare the effect of DIs in individuals with CA, CVA and COUGH using high-dose methacholine (MCh). Methods: Individuals aged 18-65 years with CA, or suspected CVA attended 3 visits. On visit 1, subjects performed body plethysmography and high-dose MCh testing to a maximum change (Δ) in FEV1 of 50% from baseline (MAX). On visits 2 and 3, subjects performed one of two modified single-dose MCh challenge tests with or without DIs prior to MCh administration. Partial and maximal-flow volume curves (used to calculated a DI index), impulse oscillometry (IOS) measurements and breathlessness (Borg scale) were recorded at baseline and at each dose of MCh. Lung volumes were measured by body plethysmography at baseline and MAX. Responses from baseline to a 20% decline in FEV1 (PC20) or MAX, and between visits with or without DIs were compared using paired t-tests. Between group differences were assessed by analysis of variance. Results: 19 subjects (14 female; 45.1±13.1 years (MEAN±SD)) completed the protocol (n=8 CA, n=7 CVA, and n=4 COUGH). At the dose nearest to PC20, the DI index was positive in all 3 groups, indicating preserved bronchodilation (CA: 0.88±0.67; CVA: 0.33±0.39; COUGH: 0.016±0.46; P=.0.076). There were no significant differences in: the Δs in spirometry, lung volumes, airway resistance, IOS measurements, closing indices, the DI index, or dyspnea when the single dose of MCh was preceded either by five DIs or by DI avoidance in CVA and COUGH. DIs in CA resulted in greater Δs in mid-to-late flows. Conclusion: The bronchodilating effect of DIs is preserved in CA, CVA and COUGH. The bronchoprotective effect may fall along a continuum. A larger study including subjects with more severe CA is required to definitively test the hypotheses. / Thesis (Master, Physiology) -- Queen's University, 2014-06-28 11:23:29.814

Thesis (Ph. D.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains xi, 100 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 80-86).

Class of 2008 Abstract / Objectives: : The purpose of this paper is to provide greater understanding of ACE inhibitor cough and appropriate treatment options. Methods: A Medline search of key terms from 1975-2008 was conducted and all types of published material were included in this review. The articles were evaluated for relevance and appropriateness for inclusion in this review. Subjects considered appropriate included ACE inhibitor cough treatment, mechanism of action, incidence and prevalence, genetics, cough characteristics, onset and resolution of cough, and others. Whenever possible, original studies were obtained but several reviews were also used. Results: ACE inhibitor cough is typically a dry, non-productive, persistent but benign cough reportedly occurring in anywhere from 0.5%-50% of patients receiving ACE inhibitors, though most studies indicate less than 20%. The mechanism is not completely understood but seems to be related to a complicated mechanism involving pathways caused by ACE inhibition and including bradykinin, C fibers, and prostaglandins. Several treatment options have been successful in resolving or relieving cough, including NSAIDs, baclofen, cromolyn and others. Results, however, are inconsistent. Anti-tussive agents, switching to a different ACE inhibitor, or lowering the dose of the current ACE inhibitor do not seem to be effective. Conclusions: In spite of its benign nature, ACE inhibitor cough is usually bothersome enough to discontinue the medication and therefore can not be ignored. Several treatments have appeared effective, all of which carry the risk of drug interactions and additional side effects, and alternative therapy such as angiotensin receptor blockers seem to be reasonable in indicated patients.

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 – 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.

published_or_final_version / Community Medicine / Master / Master of Public Health

No description available.

Introduction: Bordetella pertussis is an important human pathogen that causes whooping cough (pertussis), an endemic illness responsible of significant morbidity and mortality, especially in infants and children. Worldwide, there are an estimated of 16 million cases of pertussis, resulting in about 195,000 child deaths per year. In Peru, pertussis is a major health problem that has been on the increase despite immunization efforts. The objective of this study was to determine the prevalence of B. pertussis among children under five years of age suspected to have whopping cough in Cajamarca, Peru. Methodology: Children diagnosed with whooping cough admitted to the Hospital Regional de Cajamarca from August 2010 to July 2013 were included. Nasopharyngeal samples were obtained for B. pertussis culture and polymerase chain reaction (PCR) detection. Results: In 133 children, the pertussis toxin and IS481 gene were detected in 38.35% (51/133) of the cases by PCR, while only 9.02% (12/133) of the Bordetella cultures were positive. The most frequent symptoms in patients with positive B. pertussis were paroxysm of coughing 68.63% (35/51), cyanosis 56.86% (29/51), respiratory distress 43.14% (22/51), and fever 39.22% (20/51). Pneumonia and acute bronchial obstructive syndrome were present in 17.65% (9/51) and 13.72% (7/51) of the cases, respectively. Conclusions: B. pertussis is responsible for an important proportion of whooping cough in hospitalized children in Cajamarca. Epidemiologic surveillance programs for B. pertussis are essential in Peru, especially in children who could most benefit from the vaccine.

Objectives To report the incidence, epidemiology, and clinical features of Bordetella pertussis in Peruvian infants under 1 year old. Patients and methods A prospective cross-sectional study was conducted in five hospitals in Peru from January 2010 to July 2012. A total of 392 infants under 1 year old were admitted with a clinical diagnosis of whooping cough and tested for B. pertussis by PCR. Results The pertussis toxin and IS481 genes were detected in 39.54% (155/392) of the cases. Infants aged less than 3 months were the most affected, with a prevalence of 73.55% (114/155). The most common household contact was the mother, identified in 20% (31/155) of cases. Paroxysm of coughing (89.03%, 138/155), cyanosis (68.39%, 106/155), respiratory distress (67.09%, 104/155), and breastfeeding difficulties (39.35%, 61/155) were the most frequent symptoms reported. Conclusion An increase in pertussis cases has been reported in recent years in Peru, despite national immunization efforts. Surveillance with PCR for B. pertussis is essential, especially in infants less than 1 year old, in whom a higher rate of disease-related complications and higher mortality have been reported. / This 312 work was supported by Sanofi Aventis del Peru. Conflict 313 of interest: On behalf of all authors, the corresponding author 314 states that there are no conflicts of interest or funding related 315 to this study