Cough Response Research Articles

Continuous postoperative infusion of remifentanil inhibits the stress responses to tracheal extubation of patients under general anesthesia.

PurposeThe study aimed to assess the combined effects of parecoxib with three different doses of remifentanil and its effect on the stress and cough responses following tracheal extubation under general anesthesia.MethodsA total of 120 patients with American Society of Anesthesiologists (ASA) scores of I or II, undergoing selective thyroidectomy with total intravenous anesthesia (propofol-remifentanil) and tracheal intubation, were randomly allocated to be treated with an intravenous injection of parecoxib and a continuous infusion of remifentanil at 0.1 μg/kg/min (R1), 0.2 μg/kg/min (R2), 0.3 μg/kg/min (R3), or an isotonic saline injection (the control group). Hemodynamic vital signs, emergence time, extubation time, sedation-agitation scale (SAS) score, pain visual analog scale (VAS) score, occurrence of coughing, and side effects were recorded before surgery and during the peri-extubation period. The vital signs included blood pressure (BP), heart rate (HR), respiratory rate (R), and peripheral arterial oxygen saturation (SPO2).ResultsBP, HR, the occurrence rate of coughing, and extubation awareness decreased with the dose of remifentanil, and the differences among the groups were significant (P < 0.05). Emergence and extubation time increased with the dose of remifentanil, and the differences among the groups were significant (P < 0.05). The occurrence rates of respiratory depression and bradycardia in group R3 were significantly higher than those in other groups (P < 0.05). SAS and VAS were lowest in group R3, and the differences among the groups were significant (P < 0.05). BP, HR, SAS, and VAS increased with time in the remifentanil groups.ConclusionThe combined use of parecoxib and a moderate dose of remifentanil can effectively suppress the stress and coughing responses during the peri-extubation period. The appropriate quantity of remifentanil was found to be 0.2 μg/kg/min, as this dosage caused no side effects.

Sex Differences in Cough Responses of Cats

In humans, women are more debilitated by chronic coughing, report to physicians for cough more frequently, and have a greater cough sensitivity than men. These sex differences between men and women begin to emerge at the end of puberty. We conducted a retrospective analysis in anesthetized cats to determine if sex differences could be identified in an animal model that is capable of intense repetitive coughing. Anesthetized cats (13 males, 10 females) were tracheotomized and allowed to breathe spontaneously. Electromyograms of parasternal, transversus abdominis/internal oblique, and laryngeal adductor muscles were recorded. Esophageal pressure (Pes) was recorded via small balloon placed in the midthoracic esophagus. Cough was induced by mechanical stimulation of the intrathoracic trachea with a small polyethylene tube via the trachea cannula. We evaluated the cough response before and after a protocol consisting of 20 consecutive mechanical stimulation trials separated by approximately one minute. This adaptation protocol typically results in a depression of coughing by approximately 50% with the subsequent cough response remaining stable for extended periods of time. There was no difference in the number of trials in the adaptation protocol between males and females (20±1 males, 20±1 females). Likewise, end tidal CO2, as an index of anesthetic level, did not differ between the groups (males 31±0.5, females 32±0.8). Cough frequency (CF‐number of coughs per second) declined significantly in both male and female cats during the adaptation protocol (males control CF 1.3±0.2, post adaptation CF‐0.8±0.1, P&lt;0.001; females control CF‐1.0±0.06, post adaptation CF‐0.5±0.04, P&lt;0.001). Control CF was not significantly different between males and females (P&lt;0.2), but the post adaptation CF was higher in males (P&lt;0.05). Pes declined significantly during the adaptation protocol in both males and females (males control 50±8 cm H2O, post adaptation 26±4 cm H2O, P&lt;0.001; females control 22±3 cm H2O, post adaptation 14±3 cm H2O, P&lt;0.04). Pes was higher in males both in the control period (P&lt;0.05) and post adaptation (P&lt;0.02). However, there was no significant difference between males and females when these changes were expressed as percentages or when normalized to body weight. The results indicate that sex differences in cough responses exist in this model of cough. Differences in cough intensity between sexes can be explained by body weight. CF is a metric of peripheral sensory and/or central excitability and females exhibit greater depression of coughing in a repetitive trial protocol than males. The mechanisms responsible for this sex difference are unknown.Support or Funding InformationNIH HL 103415 and 1OT20D001983

Dexmedetomidine\u2019s inhibitory effects on acetylcholine release from cholinergic nerves in guinea pig trachea: a mechanism that accounts for its clinical benefit during airway irritation

BackgroundAirway instrumentation can evoke upper airway reflexes including bronchoconstriction and cough which can cause serious complications including airway trauma, laryngospasm or bronchospasm which may in turn lead to difficulty with ventilation and hypoxemia. These airway events are mediated in part by irritant-induced neuronal modulation of airway tone and cough responses. We investigated whether the commonly used anesthetic agents dexmedetomidine, lidocaine or remifentanil attenuated neuronal and airway smooth muscle responses in the upper airways of guinea pigs.MethodsThe ability of dexmedetomidine, lidocaine or remifentanil to attenuate direct cholinergic nerve stimulation, C-fiber stimulation or direct smooth muscle contraction were studied using isolated tracheal rings from male guinea pigs under four paradigms; (1) the magnitude of contractile force elicited by cholinergic electrical field stimulation (EFS); (2) the amount of acetylcholine released during cholinergic EFS; (3) the direct airway smooth muscle relaxation of a sustained acetylcholine-induced contraction and (4) the magnitude of C-fiber mediated contraction.ResultsDexmedetomidine (1–100 μM) and lidocaine (1 mM) attenuated cholinergic 30Hz EFS-induced tracheal ring contraction while remifentanil (10 μM) had no effect. Dexmedetomidine at 10 μM (p = 0.0047) and 100 μM (p = 0.01) reduced cholinergic EFS-induced acetylcholine release while lidocaine (10 μM-1 mM) and remifentanil (0.1–10 μM) did not. Tracheal ring muscle force induced by the exogenous addition of the contractile agonist acetylcholine or by a prototypical C-fiber analogue of capsaicin were also attenuated by 100 μM dexmedetomidine (p = 0.0061 and p = 0.01, respectively). The actual tracheal tissue concentrations of dexmedetomidine achieved (0.54–26 nM) following buffer application of 1–100 μM of dexmedetomidine were within the range of clinically achieved plasma concentrations (12 nM).ConclusionsThe α2 adrenoceptor agonist dexmedetomidine reduced cholinergic EFS-induced contractions and acetylcholine release consistent with the presence of inhibitory α2 adrenoceptors on the prejunctional side of the postganglionic cholinergic nerve-smooth muscle junction. Dexmedetomidine also attenuated both exogenous acetylcholine-induced contraction and C-fiber mediated contraction, suggesting a direct airway smooth muscle effect and an underlying mechanism for cough suppression, respectively.

Normal Saline Solution Nasal-Pharyngeal Irrigation Improves Chronic Cough Associated with Allergic Rhinitis

Upper airway inflammation is one of the most commonly identified causes of chronic cough, although the underlying mechanism is not clear. This study compared normal saline solution nasal-pharyngeal irrigation (NSNPI) and fluticasone propionate nasal spray (FPNS) treatment for chronic cough associated with allergic rhinitis (AR). Patients with suspected AR to house-dust mite were enrolled, and the symptom of cough was assessed by a cough symptom score and the Leicester Cough Questionnaire, and cough response to capsaicin was evaluated. AR was assessed by using the visual analog scale (VAS) and the Mini Juniper Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Mediators, including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein from nasal lavage fluid (NLF) were examined. The patients were treated with NSNPI (the NSNPI group) or FPNS (the FPNS group) for 30 days, after which they were reassessed. Forty-five of 50 patients completed this study. The scores of the cough symptom and the Leicester Cough Questionnaire, and the capsaicin cough threshold all improved statistically after NSNPI but did not change after FPNS. There were statistically significant changes in the evaluations of the MiniRQLQ and the mediators, including histamine and leukotriene C4, in the NLF in the NSNPI group. However, significant changes were found in the assessments of VAS, MiniRQLQ, and all above mediators including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein in the NLF of the FPNS group. Furthermore, the assessments of VAS and all the mediators were reduced more in the FPNS group compared with those in the NSNPI group. The patients with suspected AR to house-dust mite reported a better relief of the cough symptom after 30 days of treatment with NSNPI compared with that after nasal corticosteroid.

Cough and expiration reflexes elicited by inhaled irritant gases are intensified in ovalbumin-sensitized mice.

This study was designed to determine the effect of active sensitization with ovalbumin (Ova) on cough responses to inhaled irritant gases in mice. Conscious mice moved freely in a recording chamber, while the pressure change in the chamber and audio and video signals of the mouse movements were recorded simultaneously to measure the frequencies of cough reflex (CR) and expiration reflex (ER). To further verify the accuracy of cough analysis, the intrapleural pressure was also recorded by a telemetry sensor surgically implanted in the intrapleural space in a subgroup of mice. During the irritant gas inhalation challenge, sulfur dioxide (SO2; 200 and 400 ppm) or ammonia (NH3; 0.1% and 0.2%) was drawn into the chamber at a constant flow rate for 8 min. Ova sensitization and sham sensitization with vehicle (Veh) were performed over a 25-day period in separate groups of mice. Our results showed that 1) both SO2 and NH3 inhalation challenges increased CR and ER frequencies in a concentration-dependent manner before Ova sensitization; 2) the baseline CR frequency was significantly elevated after Ova sensitization, accompanied by pronounced airway inflammation; and 3) Ova sensitization also markedly augmented the responses of CR and ER to both SO2 and NH3 inhalation challenges; in sharp contrast, the cough responses did not change after sham sensitization in the Veh group. In conclusion, Ova sensitization caused distinct and lingering increases in baseline cough frequency, and also intensified both CR and ER responses to inhaled irritant gases, which probably resulted from an allergic inflammation-induced hypersensitivity of airway sensory nerves.

Does diurnal variation in cough reflex testing exist in healthy young adults?

The aim of this study was to investigate whether diurnal variation in cough reflex sensitivity exists in healthy young adults when a tidal-breathing method is used. Fifty-three participants (19–37 years) underwent cough reflex testing on two occasions: once in the morning (between 9 am – midday) and once in the afternoon (between 2–5 pm). The order of testing was counter-balanced. Within each assessment, participants inhaled successively higher citric acid concentrations via a facemask, with saline solution randomly interspersed to control for a placebo response. The lowest concentration that elicited a reflexive cough response was recorded. Morning cough thresholds (mean=0.6mol/L) were not different from afternoon cough thresholds (mean=0.6mol/L), p=0.16, T=101, r=−0.14. We found no evidence of diurnal variability in cough reflex testing. There was, however, an order effect irrespective of time of day, confirming that healthy participants are able to volitionally modulate their cough response.

Mycoplasma and Chlamydia infection related cough and bronchial responsiveness in children

Mycoplasma and Chlamydia infection related cough and bronchial responsiveness in children

Tussive challenge with ATP and AMP: does it reveal cough hypersensitivity?

Recent studies have demonstrated that blockade of P2X3 ATP receptors can profoundly inhibit chronic cough. We have considered whether inhaled ATP produces a tussive response and whether chronic cough patients are hypersensitive to inhaled ATP compared to healthy volunteers.A standardised inhalational cough challenge was performed with ATP and AMP. We randomised 20 healthy volunteers and 20 chronic cough patients as to the order of challenges. The concentration of challenge solution causing at least five coughs (C5) was compared for ATP and AMP.The study population consisted of six male and 14 female volunteers in each group. Two out of 19 healthy volunteers coughed with AMP (one volunteer could not take part in this challenge) and none reached C5. Eight out of 20 chronic cough patients coughed with AMP and two reached C5. Of the 20 healthy volunteers, 18 coughed with ATP, with 15 reaching C5. All 19 chronic cough patients completing the ATP challenge coughed with ATP and 18 reached C5. The chronic cough patients had a greater cough response at lower concentrations of ATP.The greater potency of ATP versus AMP in the inhalational challenge suggests that tussive responses are mediated through members of the P2X purinergic receptor family. This acute effect was, however, not sufficient to explain cough hypersensitivity syndrome.

To Compare the Effect of Two Different Doses of Dexmedetomidine on the Attenuation of Airway and Pressor Response during Tracheostomy Tube Change in Traumatic Brain Injury Patients.

Background:Tracheostomy tube (TT) change is the common procedure in trauma Intensive Care Unit (ICU) and almost always associated with cough reflex, increase in blood pressure, and heart rate. Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist well studied for the prevention of pressor response during laryngoscopy and extubation, but literature on prevention of pressor response during TT change is lacking.Aims:The aim of this study is to compare two doses (0.5 and 1.0 μg/kg) of DEX for prevention of cough and pressor response during TT change in traumatic brain injury patients.Settings and Design:Prospective randomized, double-blind trial.Materials and Methods:Sixty tracheostomized traumatic brain injury patients in ICU scheduled for TT change were randomized to two equal groups: Group A to receive DEX 0.5 μg/kg and Group B to receive DEX 1.0 μg/kg. Calculated dose of studied drug was given by infusion pump over 10 min after dilution in 50 ml. Hemodynamic parameters, cough reflex, and adverse event were recorded and statistically analyzed.Statistical Analysis:Statistical analysis was done with nonpaired (two tailed, independent) Student's t-test for continuous data. Demographic data were compared using Pearson's χ2 test. P < 0.05 was considered to be statistically significant.Results:Both doses of DEX were able to attenuate the hemodynamic response of tracheal stimulation and cough reflex. Cough reflex was better controlled with 1.0 μg/kg dose but associated with increased incidence of hypotension and bradycardia.Conclusions:We conclude that 0.5 μg/kg dose provides desired attenuation of hemodynamic response during TT change without any significant adverse events.

Role of gender in basic cough research

Cough hypersensitivity affects mainly postmenopausal women. Pathogenesis remains unknown in their case; therefore, an optimal treatment is unavailable. Only male guinea pigs are used in basic cough research and exclusion of females leads to gender bias. Nowadays, the efforts of grant agencies aim to support projects which take gender into account and involve both sexes to reduce gender bias. The aim of our pilot study is to assess the suitability of female guinea pig model in cough research. Cough response to citric acid (0.4M) was obtained in female and male guinea pigs (n=12 each). Reproducibility of cough response was tested four times a week apart. The cough was detected from the airflow traces and cough sound analysis. Our initial results show that cough response of female guinea pigs is higher than in males. Variability of females is also higher than in males. Further investigations are necessary to validate this model in different conditions to achieve gender equality in cough studies.

TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli

Osmolarity changes of airway superficial fluid are associated with cough and are used in research. TRPV4 is calcium channel initially described as osmosensor. In the airways, it can play role in increasing cough reflex sensitivity. The aim of our study was to test whether cough to osmotic stimuli is mediated via TRPV4 channel.Cough response was measured in 12 male guinea pigs by inhalation of saline, distilled water, hypertonic solution and citric acid for 10min in whole-body plethysmograph. Data were obtained in naïve animals and after pre-treatment with selective TRPV4 antagonist GSK2193874 in doses 300μg/kg (GSK300) and 900μg/kg (GSK900).Cough response to all tested aerosols was significantly higher than to saline. Pre-treatment with GSK300 did not influence response to osmotic stimuli − only reduced cough to citric acid. GSK900 reduced cough response to hypotonic stimuli and citric acid.TRPV4 mediated activation of airway afferents does not seem to be the exclusive mechanism responsible for cough to osmotic stimuli.

Cough reflex attenuation and swallowing dysfunction in sub-acute post-stroke patients: prevalence, risk factors, and clinical outcome.

Cough and swallowing impairments in post-stroke patients (PSP) have been associated with increased risk for respiratory complications. To assess the prevalence of alterations in protective cough responses in subacute PSP and its association with oropharyngeal dysphagia (OD), clinical, and neurotopographic stroke factors and clinical outcomes. Three months after stroke, the cough reflex test (CRT) was performed by nebulizing incremental citric acid concentrations (7.8-1000mmolL-1 ) to determine the concentration that elicited two and five coughs; OD was assessed by the volume-viscosity swallow test. Clinical and neurotopographic stroke risk factors and complications (readmissions, respiratory infections, institutionalization, and mortality) were recorded from 3 to 12months post-stroke. We included 225 PSP. Prevalence of impaired CRT was 5.8%, that of OD was 40.4% (20.4% with impaired safety of swallow), and of both impairments was, 1.8%. No specific risk factors associated with impaired CRT were found; however, hemorrhagic, wide circulation infarction (TACI), and brainstem strokes delayed the cough response. OD was associated with age, TACI and poor functional and nutritional status. Outcome of PSPs was unaffected by impaired CRT but OD and impaired safety of swallow increased institutionalization, respiratory infections, and mortality with the poorest outcome for those with both impairments. Prevalence of subacute post-stroke OD and swallow safety impairments was much higher than CRT attenuation, and risk factors strongly differed suggesting that the swallow response receives a stronger cortical control than the cough reflex. OD has a greater impact on PSP clinical outcome than impaired cough, the poorest prognosis being for patients with both airway protective dysfunctions.

Effects of intravenous and topical laryngeal lidocaine on heart rate, mean arterial pressure and cough response to endotracheal intubation in dogs

ObjectiveTo compare the effects of intravenous (IV) and topical laryngeal lidocaine on heart rate (HR), mean arterial pressure (MAP) and cough response to endotracheal intubation (ETI) in dogs. Study designProspective, randomized, blinded clinical study. AnimalsForty-two client-owned dogs (American Society of Anesthesiologists class I and II status) undergoing elective orthopaedic surgery. MethodsDogs were randomized to three groups. Dogs in group SALIV received 0.1 mL kg−1 IV saline. Dogs in group LIDIV received 2 mg kg−1 IV 2% lidocaine. Dogs in group LIDTA received 0.4 mg kg−1 topically sprayed laryngeal 2% lidocaine. All dogs were premedicated with methadone (0.2 mg kg−1 IV). After 30 minutes, IV propofol was administered to abolish the lateral palpebral reflex and produce jaw relaxation. The allocated treatment was then administered and, after 30 seconds, further propofol was administered to abolish the medial palpebral reflex and facilitate ETI. HR and MAP were measured at four time-points using cardiac auscultation and automated oscillometry, respectively. The cough response at ETI was recorded. One-way anova and post hoc Tukey adjustment were used to analyse parametric data. The Kruskal-Wallis test was used to analyse non-parametric data. Odds ratios were calculated for the cough response. A p-value of =0.05 was considered to indicate statistical significance. ResultsIn response to ETI, changes in MAP differed significantly between groups. In SALIV, MAP increased (4 ± 6 mmHg), whereas it decreased in LIDIV (6 ± 13 mmHg) (p= 0.013) and LIDTA (7 ± 11 mmHg) (p= 0.003). Dogs in SALIV were almost 10 times more likely to cough than dogs in LIDIV (odds ratio 9.75, 95% confidence interval 0.98–96.60; p = 0.05). Conclusions and clinical relevanceIn propofol-anaesthetized dogs, IV and topical laryngeal lidocaine attenuated the pressor response to ETI, whereas IV lidocaine reduced the cough response.

Effect of intravenous lidocaine on cough response to endotracheal intubation in propofol-anaesthetized dogs

ObjectiveTo determine whether the administration of intravenous (IV) lidocaine before the induction of anaesthesia in premedicated dogs reduces the cough response associated with endotracheal intubation and the propofol dose required. Study designProspective, randomized, blinded clinical study. AnimalsA total of 84 client-owned dogs, with American Society of Anesthesiology physical status I and II. MethodsDogs received intramuscular (IM) acepromazine 0.02 mg kg−1 and methadone 0.3 mg kg−1 and were randomly allocated to one of two groups: saline (group S) and lidocaine (group L). Five minutes before the induction of anaesthesia and 40–50 minutes after premedication, group L received lidocaine (1.5 mg kg−1) and group S received an equal volume of saline solution, each administered slowly IV. Anaesthesia was induced with propofol, initially 2 mg kg−1 IV over 40 seconds, and then in increments of 0.5 mg kg−1 every 15 seconds to effect. The same investigator anaesthetized all cases, unaware of group allocation. The following parameters were recorded: pulse rate (PR), mean arterial pressure (MAP, oscillometry), respiratory rate (fR), sedation score immediately before and 5 minutes after treatment, and total dose of propofol required. Differences in pulse rate, MAP and propofol dose were analysed using the two-sample t-test, coughing incidence was analysed with the chi-square test, and differences in sedation score were analysed with the Mann–Whitney test. ResultsAfter treatment, the incidence of coughing at endotracheal intubation was significantly reduced in group L compared with group S (21% versus 45%; p=0.022). There was no significant difference between the groups with regard to propofol dose required for endotracheal intubation (p=0.122), PR (p=0.611), MAP (p=0.508) or sedation score (p=0.051). Conclusions and clinical relevanceIV lidocaine can decrease the incidence of cough during endotracheal intubation in dogs premedicated with acepromazine and methadone, but does not appear to have a sparing effect on the dose of propofol required for endotracheal intubation. Use of IV lidocaine, prior to induction of anaesthesia with propofol may be beneficial in dogs where coughing at intubation would be detrimental.

Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies.

Most airway diseases, including chronic obstructive pulmonary disease (COPD), are associated with excessive coughing. The extent to which this may be a consequence of increased activation of vagal afferents by pathology in the airways (e.g., inflammatory mediators, excessive mucus) or an altered neuronal phenotype is unknown. Understanding whether respiratory diseases are associated with dysfunction of airway sensory nerves has the potential to identify novel therapeutic targets. To assess the changes in cough responses to a range of inhaled irritants in COPD and model these in animals to investigate the underlying mechanisms. Cough responses to inhaled stimuli in patients with COPD, healthy smokers, refractory chronic cough, asthma, and healthy volunteers were assessed and compared with vagus/airway nerve and cough responses in a cigarette smoke (CS) exposure guinea pig model. Patients with COPD had heightened cough responses to capsaicin but reduced responses to prostaglandin E2 compared with healthy volunteers. Furthermore, the different patient groups all exhibited different patterns of modulation of cough responses. Consistent with these findings, capsaicin caused a greater number of coughs in CS-exposed guinea pigs than in control animals; similar increased responses were observed in ex vivo vagus nerve and neuron cell bodies in the vagal ganglia. However, responses to prostaglandin E2 were decreased by CS exposure. CS exposure is capable of inducing responses consistent with phenotypic switching in airway sensory nerves comparable with the cough responses observed in patients with COPD. Moreover, the differing profiles of cough responses support the concept of disease-specific neurophenotypes in airway disease. Clinical trial registered with www.clinicaltrials.gov (NCT 01297790).

Capsaicin-evoked cough responses in asthmatic patients: Evidence for airway neuronal dysfunction

Cough in asthmatic patients is a common and troublesome symptom. It is generally assumed coughing occurs as a consequence of bronchial hyperresponsiveness and inflammation, but the possibility that airway nerves are dysfunctional has not been fully explored. We sought to investigate capsaicin-evoked cough responses in a group of patients with well-characterized mild-to-moderate asthma compared with healthy volunteers and assess the influences of sex, atopy, lung physiology, inflammation, and asthma control on these responses. Capsaicin inhalational challenge was performed, and cough responses were analyzed by using nonlinear mixed-effects modeling to estimate the maximum cough response evoked by any concentration of capsaicin (Emax) and the capsaicin dose inducing half-maximal response (ED50). Ninety-seven patients with stable asthma (median age, 23years [interquartile range, 21-27years]; 60% female) and 47 healthy volunteers (median age, 38years [interquartile range, 29-47years]; 64% female) were recruited. Asthmatic patients had higher Emax and lower ED50 values than healthy volunteers. Emax values were 27% higher in female subjects (P=.006) and 46% higher in patients with nonatopic asthma (P=.003) compared with healthy volunteers. Also, patients with atopic asthma had a 21% lower Emax value than nonatopic asthmatic patients (P=.04). The ED50 value was 65% lower in female patients (P=.0001) and 71% lower in all asthmatic patients (P=.0008). ED50 values were also influenced by asthma control and serum IgE levels, whereas Emax values were related to 24-hour cough frequency. Age, body mass index, FEV1, PC20, fraction of exhaled nitric oxide, blood eosinophil counts, and inhaled steroid treatment did not influence cough parameters. Patients with stable asthma exhibited exaggerated capsaicin-evoked cough responses consistent with neuronal dysfunction. Nonatopic asthmatic patients had the highest cough responses, suggesting this mechanism might be most important in type 2-low asthma phenotypes.

Stepping down from combination asthma therapy: The predictors of outcome

BackgroundStepping down from combination asthma therapy (inhaled corticosteroids (ICS) + long-acting β2 agonists (LABA)) is often avoided due to fear of exacerbations, which may lead to overmedication in well-controlled asthma. A better knowledge about the predictors of outcome might encourage clinicians to start stepping down more often than previously. MethodsIn 55 subjects with well controlled asthma and combination therapy, LABAs were discontinued first, followed by ICS dose halving, and then cessation, in six weeks’ intervals. The ability of Juniper’s asthma control questionnaire (ACQ), ambulatory peak flow monitoring, spirometry, and hypertonic saline challenge to predict the outcomes of medication reductions were assessed. ResultsThe proportions of subjects experiencing an exacerbation at each step were: 4 out of 55 subjects (7%) after LABA cessation, 4 out of 25 subjects (16%) after ICS dose halving, and 21 out of 46 subjects (46%) after ICS cessation. All exacerbations could be managed on an outpatient basis. There were 126 step-downs altogether. ACQ score < 0.29 (likelihood ratio 2.30 (1.05–5.05)), ACQ without spirometry < 0.15 (2.17 (0.96–4.90)) and FEV1 > 96% of predicted (2.18 (1.03–4.61)) predicted a successful outcome after step-down. Cough responsiveness to saline, bronchoconstrictive responsiveness to saline, and peak flow variation were not associated with the outcome. ConclusionCombination therapy can often be reduced in controlled asthma but total cessation of ICSs must be carefully considered. Simple investigations, namely asthma control assessment by validated questionnaire and spirometry, help to predict the outcome of stepping down. Trial registryThe study was registered in ClinicalTrials.gov database (https://clinicaltrials.gov, KUH5801124).

PTU-126 High Incidence of Oesophageal Dysmotility and Increased Inspiratory Gastro-Oesophageal Pressure Gradients in Patients with Unexplained Respiratory Symptoms

Introduction It has been suggested that reflux and aspiration are common precipitants in respiratory diseases such as cough, asthma and Chronic Obstructive Pulmonary Disease. An excess of acid in these patients has been demonstrated by conventional pH monitoring, but correlation with symptoms are relatively poor. We have previously hypothesised that oesophageal dysmotility leading to both acid and non-acid aspiration may be an important etiological mechanism. Studies have also highlighted the importance of the gastro-oesophageal pressure gradient (GOPG) in the prevalence of reflux. 1 Methods High Resolution Oesophageal Manometry (HRM) was performed in 121 patients, 61 of whom presented primarily with unexplained respiratory symptom and complained predominantly of chronic cough (50), or breathlessness (11). An age and sex matched control group was chosen from patients presenting with suspected gastro-oesophageal reflux disease (GORD). The HRM findings of 61 patients (38 female), mean age 56 (range 18–81) with respiratory symptoms were compared with those of 60 suspected GORD patients (39 female), mean age 57, (range 19–81). Results Mean lower oesophageal sphincter (LOS) and upper oesophageal sphincter (UOS) resting pressures were similar between the two groups. There were fewer intact swallows in the respiratory group compared to those of the GORD group (42% vs 57%, P = 0.03). Intraoesophageal pressure was significantly lower during inspiration in the respiratory group compared to those of the GORD group (-11.5mmHg vs -8.7, p = 0.001). Consequently, there was a significantly higher GOPG was found in respiratory patients compared to those of the GORD group (46 mmHg vs 33 mmHg, p Conclusion Using High Resolution Oesophageal Manometry, we have demonstrated a higher prevalence of oesophageal dysmotility in patients with unexplained respiratory symptoms than those presenting with typical GORD. Moreover, we have shown that those with unexplained respiratory symptoms exhibit higher inspiratory GOPGs and greater LOS peak contractions possibly stimulating an afferent vagal cough response. Reference 1 Ayazi S, DeMeester SR, et al . Thoracic-abdominal pressure gradients during the phases of respiration contribute to gastroesophageal reflux disease. Digestive Disease and Sciences 2011; 56 :1718–22. Disclosure of Interest None Declared

Bronchoconstriction-triggered cough in atopic cough: A retrospective study

ABSTRACTBackground: Atopic cough (AC) and cough variant asthma (CVA) were identified as major causes of chronic non-productive cough in a Japanese study. A characteristic feature of CVA is the presence of a heightened cough response to bronchoconstriction. On the other hand, the cough response to bronchoconstriction in AC remains unclear. Methods: Methacholine (Mch)-induced cough in AC was measured and compared with that in CVA. Diagnoses of AC and CVA were made based on patient history, physical examination, response to bronchodilator therapy, cough reflex sensitivity to capsaicin, spirometry, and airway responsiveness to methacholine. Results: Thirteen AC patients and 12 CVA patients in whom the criteria were met were recruited to the study. After inhalation of Mch at PC35-PEF40 that means milder bronchoconstriction than PC20-FEV1, cough was triggered a few times in AC. [cough number: 1/ 32 min (0–40)]. Conversely, significantly greater number of coughs was provoked in CVA, compared with AC [cough number: 35.5/ 32 min (25-125), p < 0.05]. Conclusions: The cough response to bronchoconstriction is reduced in AC compared to CVA. This feature may be useful in the diagnosis of chronic cough.

Rehabilitation of Swallowing and Cough Functions Following Stroke: An Expiratory Muscle Strength Training Trial

ObjectiveTo determine the effect of expiratory muscle strength training (EMST) on both cough and swallow function in stroke patients. DesignProspective pre-post intervention trial with 1 participant group. SettingTwo outpatient rehabilitation clinics. ParticipantsAdults (N=14) with a history of ischemic stroke in the preceding 3 to 24 months. InterventionEMST. The training program was completed at home and consisted of 25 repetitions per day, 5 days per week, for 5 weeks. Main Outcome MeasuresBaseline and posttraining measures were maximum expiratory pressure, voluntary cough airflows, reflex cough challenge to 200μmol/L of capsaicin, sensory perception of urge to cough, and fluoroscopic swallow evaluation. Repeated measures and 1-way analyses of variance were used to determine significant differences pre- and posttraining. ResultsMaximum expiratory pressure increased in all participants by an average of 30cmH2O posttraining. At baseline, all participants demonstrated a blunted reflex cough response to 200μmol/L of capsaicin. After 5 weeks of training, measures of urge to cough and cough effectiveness increased for reflex cough; however, voluntary cough effectiveness did not increase. Swallow function was minimally impaired at baseline, and there were no significant changes in the measures of swallow function posttraining. ConclusionsEMST improves expiratory muscle strength, reflex cough strength, and urge to cough. Voluntary cough and swallow measures were not significantly different posttraining. It may be that stroke patients benefit from the training for upregulation of reflex cough and thus improved airway protection.