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Impaired urge-to-cough in elderly patients with aspiration pneumonia
Background:
The down-regulation of the cough reflex in patients with aspiration pneumonia can involve both cortical facilitatory pathways for cough and medullary reflex pathways. In order to study the possible involvement of the supramedullary system in the down-regulation of cough reflex, we evaluated the urge-to-cough in patients with aspiration pneumonia.
Methods:
Cough reflex sensitivity and the urge-to-cough to inhaled citric acid were evaluated in patients with at least a history of aspiration pneumonia and age-matched healthy elderly people. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough scores at the concentration of C2 and C5, and at the concentration of two times dilution of C2 (C2/2) and C5 (C5/2) were estimated for each subject.
Results:
Both C2 and C5 in the control subjects were significantly greater than those for patients with aspiration pneumonia. There were no significant differences in the urge-to-cough at C2 and C5 between control subjects and patients with aspiration pneumonia. However, the urge-to-cough scores at both C2/2 and C5/2 in patients with aspiration pneumonia were significantly lower than those in control subjects. The number of coughs at C5/2 was significantly greater in the control subjects than those in the patients with aspiration pneumonia whereas the number of coughs at C2/2 did not show a significant difference between the control subjects and the patients with aspiration pneumonia.
Conclusions:
The study suggests the involvement of supramedullary dysfunction in the etiology of aspiration pneumonia in the elderly. Therefore, restoration of the cough motivation system could be a new strategy to prevent aspiration pneumonia in the elderly.
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The utility of the mannitol challenge in the assessment of chronic cough: a pilot study
There is a need for more objective outcome measures for chronic cough. In this pilot study we sought to investigate the utility of the mannitol challenge as a cough-provocation test in non-asthmatic chronic cough. We studied 16 healthy controls and 13 subjects with chronic cough. We assessed cough severity using a visual analogue score, capsaicin cough sensitivity, health status using the Leicester Cough Questionnaire and the dose of mannitol to cause 2 (C2) or 5 (C5) coughs. In all of the subjects with chronic cough and 6 of the controls we assessed the 1-week repeatability of the mannitol challenge. We found that in those subjects with chronic cough the geometric mean (logSEM) mannitol C2 and C5 was heightened compared to controls (C2: 4 (0.2) versus 16 (0.1); p=0.04 and C5: 63 (0.1) versus 251 (0.1); p=0.04). Cough visual analogue score, capsacin-induced cough sensitivity and health status were also altered in chronic cough compared to healthy controls, but in those subjects with chronic cough none of these outcomes was correlated with the mannitol C2 or C5. The repeatability of the mannitol challenge assessed by intraclass correlation was C2=0.53 and C5=0.59. A cut-off in the dose of mannitol of 62mg/ml for C2 and 550mg/ml for C5 had a sensitivity of 69 and 62% and specificity of 69 and 81% respectively to distinguish chronic coughers from healthy controls. In conclusion, the mannitol challenge may have potential as a novel cough challenge test and further work is required to extend our findings and to assess whether it has utility in different causes of chronic cough.
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Immunohistochemical characterization of nodose cough receptor neurons projecting to the trachea of guinea pigs
Background:
Cough in guinea pigs is mediated in part by capsaicin-insensitive low threshold mechanoreceptors (cough receptors). Functional studies suggest that cough receptors represent a homogeneous population of nodose ganglia-derived sensory neurons. In the present study we set out to characterize the neurochemical profile of cough receptor neurons in the nodose ganglia.
Methods:
Nodose neurons projecting to the guinea pig trachea were retrogradely labeled with fluorogold and processed immunohistochemically for the expression of a variety of transporters (Na+/K+/2C1- co-transporter (NKCC1), a1 and a3 Na+/K+ ATPase, vesicular glutamate transporters (vGlut)1 and vGlut2), neurotransmitters (substance P, calcitonin gene-related peptide (CGRP), somatostatin, neuronal nitric oxide synthase (nNOS)) and cytosolic proteins (neurofilament, calretinin, calbindin, parvalbumin).
Results:
Fluorogold labeled ~3 per cent of neurons in the nodose ganglia with an average somal perimeter of 137 +/- 6.2 mm (range 90-200mm). All traced neurons (and seemingly all nodose neurons) were immunoreactive for NKCC1. Many (>90 per cent) were also immunoreactive for vGlut2 and neurofilament and between 50 and 85 per cent expressed a1 ATPase, a3 ATPase or vGlut1. Cough receptor neurons that did not express the above markers could not be differentiated based on somal size, with the exception of neurofilament negative neurons which were significantly smaller (P<0.05). Less than 10 per cent of fluorogold labeled neurons expressed substance P or CGRP (and these had somal perimeters less than 110mm) and none expressed somatostatin, calretinin, calbindin or parvalbumin. Two distinct patterns of nNOS labeling was observed in the general population of nodose neurons: most neurons contained cytosolic clusters of moderately intense immunoreactivity whereas less than 10 per cent of neurons displayed uniform intensely fluorescent somal labeling. Less than 3 per cent of the retrogradely traced neurons were intensely fluorescent for nNOS (most showed clusters of nNOS immunoreactivity) and nNOS immunoreactivity was not expressed by cough receptor nerve terminals in the tracheal wall.
Conclusions:
These data provide further insights into the neurochemistry of nodose cough receptors and suggest that despite their high degree of functional homogeneity, nodose cough receptors subtypes may eventually be distinguished based on neurochemical profile.
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Simultaneous versus video counting of coughs in hypertonic cough challenges
Background:
The coughs occurring during cough provocation tests are usually counted at the same time when the test is being conducted, i.e., simultaneously. It is unknown whether cough counting from video recording might increase the accuracy of the cough counting. During recent years, cough challenges with hypertonic aerosols have been introduced. They often provoke very frequent coughing which may complicate the simultaneous cough counting.ObjectiveTo assess whether cough counting from video recording is superior to simultaneous cough counting in two different hypertonic cough challenges.
Methods:
The analysis includes 82 hypertonic saline challenges performed on 66 subjects, providing 1984 observation minutes with both simultaneous and video cough counting. The cough sensitivity was expressed as the osmolality to provoke 15 cumulative coughs (CUM15). The analysis also includes 136 hypertonic histamine challenges performed on 114 subjects providing 5373 observation minutes with both simultaneous and video counting. The cough sensitivity was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). This challenge involved several additional measurements to cough counting.
Results:
For the saline challenge, the mean difference between the counting types was 0.0 coughs per minute with 95% limits of agreement of -1.2 to 1.2 coughs per minute. For the hypertonic histamine challenge the respective figures were 0.3 (-1.9 to 2.5) coughs per minute. At high coughing frequency the video counts tended to outnumber the simultaneous counts. The counting type had no effect on the hypertonic saline CUM15 and only a marginal effect on its repeatability. On the contrary, video counting resulted to significantly higher hypertonic histamine CCR values than simultaneous counting (p < 0.001).
Conclusion:
The agreement between simultaneous and video counting of coughs is generally good. However, as the coughing frequency increases, simultaneous counting may miss coughs, especially if the nurse has to share his/her attention to several activities simultaneously. Video recording is advisable for the hypertonic histamine challenge but unnecessary for the hypertonic saline challenge. To ensure reliable simultaneous cough counting, cough provocation tests should be performed in a quiet environment, applying as little unnecessary equipment and measurements as possible.
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Extrathoracic airway hyperresponsiveness as a mechanism of post infectious cough: case report
Post-infectious cough is a common diagnosis in people with chronic cough. However, the specific infectious aetiology and cough mechanisms are seldom identified.We report a case of chronic cough after Mycoplasma pneumoniae lower respiratory tract infection with extrathoracic airway hyperresponsiveness as the cough mechanism. Extrathoracic airway hyperresponsiveness may be a common mechanism in post-infectious cough which may be useful both diagnostically and therapeutically since chronic cough with extrathoracic airway hyperresponsiveness responds to speech pathology treatment.
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Achalasia: unusual cause of chronic cough in children
Achalasia is a rare motility disorder of the esophagus which results from lack of enervation of the lower esophageal sphincter muscles and leads to dilatation of proximal esophagus. Patients with achalasia presents typically with dysphagia, vomiting of undigested food and failure to thrive. Cough can be present in achalasia patients due to aspiration of food or due to airway compression by the dilated esophagus. We report two cases of achalasia presenting primarily with prolonged cough. Diagnosis of achalasia in both cases was delayed due to this atypical presentation. This highlights the importance of recognizing achalasia as a potential cause of chronic cough in order to avoid delayed diagnosis and mismanagement.
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Gastroesophageal reflux-associated chronic cough in an adolescent and the diagnostic implications: a case report
A 15-year-old girl was referred with a 2-year history of perennial non-productive cough, which had been preceded by Mycoplasma pneumoniae pneumonia and subsequent asthma. Symptoms were only partially responsive to anti-asthma treatment including an inhaled corticosteroid and a leukotriene receptor antagonist. The patient's BMI was 27.8; she had gained over 10 kg in the previous two years. Typical symptoms of gastroesophageal reflux disease were not evident except for belch. Coughing worsened on eating and rising from bed. Although esophagography failed to disclose reflux esophagitis, esophageal pH monitoring revealed significant acid reflux. Asthma was considered well controlled. Treatment with the proton-pump inhibitor rabeprazole resulted in disappearance of cough. Frequency Scale for the Symptoms of Gastroesophageal reflux disease (FSSG) score, a questionnaire evaluating the symptoms of gastroesophageal reflux disease, was initially high but normalized after treatment. Capsaicin cough sensitivity also diminished with treatment.Chronic cough due to gastroesophageal reflux disease has been considered rare in adolescents, but this condition might be increasing in line with the recent trend in adults. Clinical features of gastroesophageal reflux disease-associated cough typical for adult patients and a specific questionnaire for evaluating gastroesophageal reflux disease validated in adults may also be useful diagnostic clues in adolescents.
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Tracheobronchopathia osteochondroplastica: A rare cause of chronic cough with haemoptysis
A case of tracheobronchopathia osteochondroplastic (TPO) was diagnosed in a 69-year old male with prolonged cough. TPO is a rare condition of unknown cause and only sporadic cases have been reported. The condition is benign, characterized by submucosal nodules growing from the submucosal layer of the airways, protruding into the bronchial lumen. The bronchscopic view together with bronchial cartilage with abnormal distributed mineralization of the histologic examination of theses nodules leads to the correct diagnosis. Mild cases are treated symptomatically, whereas we tried an inhaled corticosteroid. Prominent protrusions in the trachea or the bronchi must be removed. In most cases the disease is stable over years but progressive forms have been reported. TPO may cause chronic refractory cough, which eventually is the only prominent symptom of this disease.
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The effects of Tween-80 on the integrity of solutions of capsaicin: useful information for performing tussigenic challenges
Background:
Because variable results of capsaicin challenges may be due to the incomplete solubility of capsaicin, we sought to determine if the use of Tween-80 in solutions of capsaicin improves actual concentrations of freshly prepared and stored solutions.
Methods:
Capsaicin solutions ranging from 0.5–128 μM were mixed with and without Tween-80. Samples of various concentrations were then stored under 4 environmental conditions: 4°C, protected from light; room temperature, protected from light; room temperature, exposed to light; -20°C. All samples were analyzed initially, and at 2 and 4 months.
Results:
While freshly prepared solutions with Tween-80 had consistently higher concentrations than those prepared without Tween-80 (83% vs. 69%), Tween-80 does not facilitate complete solubility. For solutions stored at 4°C and protected from light, there was a significant decrease after 2 months in low concentration solutions of both the Tween-80 and non-Tween-80 solutions. Both Tween-80 and non-Tween-80 containing solutions significantly decreased in concentration after 2 months when stored at room temperature and protected from light, room temperature and exposed to light, and -20°C. Concentrations of solutions made of 4 μM or higher are stable when stored at 4°C and protected from light for 4 months.
Conclusion:
While the inherent difficulty of forcing capsaicin into solution cannot be eliminated, it can be improved with Tween-80. However, the addition of Tween-80 does not prevent the breakdown of stored capsaicin solutions. We recommend preparing and storing capsaicin solutions according to the methods and results of this study.
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Intra-abdominal Pressures during Voluntary and Reflex Cough
Background:
Involuntary coughing such as that evoked from the larynx, the laryngeal cough reflex (LCR), triggers a coordinated contraction of the thoracic, abdominal and pelvic muscles, which increases intra-abdominal pressure (IAP), displaces the diaphragm upwards and generates the expiratory force for cough and airway clearance. Changes in the IAP during voluntary cough (VC) and the LCR can be measured via a pressure catheter in the bladder. This study evaluated the physiological characteristics of IAP generated during VC and the LCR including peak and mean pressures and calculations of the area under the curve (AUC) values during the time of the cough event or epoch.
Methods:
Eleven female subjects between the ages of 18 and 75 underwent standard urodynamic assessment with placement of an intravesicular catheter with a fiberoptic strain gauge pressure transducer. The bladder was filled with 200 ml of sterile water and IAP recordings were obtained with VC and the induced reflex cough test (RCT) using nebulized inhaled 20% tartaric acid to induce the LCR. IAP values were used to calculate the area under the curve (AUC) by the numerical integration of intravesicular pressure over time (cm H2O·s).
Results:
The mean (± SEM) AUC values for VC and the LCR were 349.6 ± 55.2 and 986.6 ± 116.8 cm H2O·s (p < 0.01). The mean IAP values were 45.6 ± 4.65 and 44.5 ± 9.31 cm H2O (NS = .052), and the peak IAP values were 139.5 ± 14.2 and 164.9 ± 15.8 cm H2O (p = 0.07) for VC and LCR, respectively.
Conclusion:
The induced LCR is the involuntary rapid and repeated synchronous expiratory muscle activation that causes and sustains an elevated IAP over time, sufficient for airway protection. VC and LCR have different neurophysiological functions. Quantification of the LCR using AUC values and mean or peak IAP values may be useful as a clinical tool for determining neurophysiological airway protection status and provide a quantitative assessment of changes in a patient's functional recovery or decline.
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