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Expiratory muscle strength training in persons with multiple sclerosis having mild to moderate disability: effect on maximal expiratory pressure, pulmonary function, and maximal voluntary cough.

OBJECTIVE: To determine the effect of expiratory muscle strength training (EMST) on maximal expiratory strength, pulmonary function, and maximal voluntary cough in persons with multiple sclerosis (MS) having mild to moderate disability. DESIGN: Before-after trial. SETTING: Assessments were completed in the privacy of the subject's home or exercise physiology laboratory. PARTICIPANTS: Seventeen persons with MS were age- and sex-matched to 14 healthy controls. INTERVENTION: Eight weeks of EMST and 4 weeks of detraining. MAIN OUTCOME MEASURES: Maximal respiratory pressures, pulmonary function, and maximal voluntary cough were assessed 3 times (pretraining, posttraining, detraining). Maximal expiratory pressure (MEP) was assessed weekly and training intensity adjusted based on the new measurement. RESULTS: Subjects with MS had lower MEP, decreased pulmonary function, and weaker maximal voluntary cough at each assessment. EMST increased MEP and peak expiratory flow. However, improvement in maximal voluntary cough only occurred in subjects with a moderate level of disability when the MS group was subdivided into mild and moderate disability levels based on the Expanded Disability Status Scale. CONCLUSIONS: EMST is a viable tool to enhance the strength of the respiratory muscles. However, further work is needed to determine the best parameters to assess change in cough following EMST.

Adult↗

Persistent cough following pulmonary resection: observational and empiric study of possible causes.

BACKGROUND: Following thoracic surgery, patients often suffer from persistent coughing. There is speculation regarding the cause. However, since few studies of that following pulmonary resection have been reported, we conducted an observational and empiric study of this issue. METHODS: A cross-sectional assessment of 240 patients who had undergone a pulmonary resection was performed using a questionnaire regarding postsurgical persistent coughing. Further, therapy based on empiric results was given to 20 patients who had undergone a lobectomy and mediastinal lymph node resection for nonsmall cell lung cancer. RESULTS: Seventy patients were surveyed within 1 year following surgery (subchronic phase), of whom 35 (50%) suffered from coughing, as compared to 30 (18%) of 170 whose postoperative time was 1 year or more (p < 0.0001). Presence of lung cancer, mediastinal lymph node resection, and gastroesophageal reflux (GER) symptoms were significant factors in the group of subchronic patients. Of the 20 patients who received empiric therapy, 90% saw their coughing symptoms improve after the course of medication. CONCLUSIONS: In the present patients, mediastinal lymph node resection may have contributed to coughing after the procedure, which tended to improve after 1 year following the operation. Further, a secondary change, such as GER, caused by surgical intervention may also be a contributing factor in the subchronic phase.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Cost-effectiveness of different diagnostic strategies to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough in Italy.

BACKGROUND: Chronic persistent cough is a common and disabling disorder and gastro-oesophageal reflux disease is considered to be the third leading cause, after asthma and postnasal drip. Therefore, patients with unexplained chronic persistent cough usually undergo a stepwise evaluation to establish the existence of a reflux disease. AIM: To identify the most cost-effective diagnostic approach to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough. METHODS: Direct and indirect costs associated with six diagnostic strategies using 24-h oesophageal pH-metry, oesophago-gastroduodenoscopy and the proton pump inhibitors test in different sequences, were evaluated using a decision tree model. If the first test was positive, the diagnostic work-up was stopped, if negative the patient proceeded to the second test, and so on. Clinical data from an observational prospective trial conducted in 51 patients with unexplained chronic persistent cough were used in the economic model. RESULTS: All six strategies had the same clinical effectiveness (78.4%). The diagnostic work-up with the lowest cost was the proton pump inhibitors test followed by pH-metry and then oesophago-gastroduodenoscopy with a total cost of euro 211.08 (direct euro 142.93, indirect euro 68.15). CONCLUSIONS: This study shows that the lowest cost is the strategy where proton pump inhibitors test is performed as first investigation. Implementation of this diagnostic work-up may lead to cost savings in the management of patients with chronic persistent cough.

Chronic Disease↗

Paroxysmal cough injury, vascular rupture and 'shaken baby syndrome'.

It is widely assumed that subdural and retinal haemorrhage in infants can only result from traumatic rupture of vulnerable blood vessels. An alternative aetiology, that of vascular rupture resulting from excessive intraluminal pressure, is presented in three disease conditions. (1) Perlman et al., studying premature neonates requiring mechanical ventilation for respiratory distress syndrome, observed "cough-like" fluctuations in oesophageal pressure greater than 18 cms H2O, whose timing matched fluctuations in anterior cerebral artery flow. When 14 out of 24 neonates were paralysed (to prevent abdominal muscle activity) intraventricular haemorrhage developed in all 10 controls but in only one of the paralysed group during paralysis. (2) New analysis of pressure data extracted from a previous study of prolonged expiratory apnoea showed alveolar collapse induced 100 mmHg intrathoracic cough pressure surges. Superior vena cava pressures up to 50 mmHg were implied, and radial artery systolic pressures over 180 mmHg recorded. (3) Bordetella pertussis bacteria attach to cilia in the airways, but do not invade the underlying tissue. The irritation causes the powerful coughing paroxysms of whooping cough. Brain haemorrhages and retinal detachment have been observed to result from the high intravascular pressures produced. The data suggest that any source of intense airway irritation not easily removed (laryngeal infection, inhalation of regurgitated feed, fluff, smoke etc.) could induce similar bleeding, a paroxysmal cough injury (PCI). Additional objective evidence of inflicted trauma is necessary to distinguish between 'shaken baby syndrome' and PCI.

Blood Vessels↗

Chronic cough: state-of-the-art review.

Cough is the most common presenting complaint in adults seeking medical treatment in an ambulatory setting. Chronic cough (persisting greater than 3 weeks) can be associated with myriad diseases that may overlap multiple medical specialties. For this reason, a thorough assessment of the patient with chronic cough relies on a multidisciplinary approach and close cooperation between pulmonary medicine, gastroenterology, and otolaryngology. Despite this daunting task, success can be achieved in up to 90% of patients with chronic cough if a systematic and thorough approach is used. The purpose of this review is to summarize the state-of-the-art in the diagnosis and treatment of chronic cough for the practicing otolaryngologist.

Ambulatory Care↗

Does post-nasal drip cause cough in childhood?

The proposition that post-nasal drip (PND) is a common cause of cough in childhood is controversial. The concept of PND as a common cause of cough is derived primarily from the adult literature. The definition of what constitutes PND is variable and it is unclear whether it is a symptom, a sign or both. Examination of the specificity of symptoms and signs for the diagnosis of PND syndrome further confuses the issue. A definitive diagnosis of cough induced by PND cannot be made from history and physical examination alone. The concept is inconsistent both with the meaning of the word 'drip' and the science of rheology. The most plausible explanation for the occurrence of cough in children identified with increased post-nasal secretions is that both reflect co-existent airways pathologies. In considering causes of chronic cough in childhood, it is now time to abandon the concept of PND and the associated PND syndrome.

Adolescent↗

Habit cough: assessment and management.

Habit cough is a condition that is often misdiagnosed as asthma. The cough is bizarre in nature, troublesome to those around the person coughing and clearly a waking phenomenon. Often, relatives will have considered the possibility of a habit cough by the time that they present to the respiratory or general paediatrician. In the majority of cases, simple explanation of the nature of likely stressors and reassurance form the basis of effective therapy. In young people with more entrenched symptoms, the provision of coping strategies and increasing the subjective sense of control is an intervention in itself and will improve the likelihood of a good outcome. In more extreme cases, the role of rehabilitation programmes involving negotiation with schools and community organisations may prove useful in remediation of the cough and normalisation of social and peer supports.

Adolescent↗

Experimental models and mechanisms of enhanced coughing.

Enhanced coughing can be produced in a variety of animal models, including the guinea pig, cat, dog and pig. Typically, airway inflammation has been produced by sensitization, exposure to cigarette smoke, sulphur dioxide or angiotensin-converting enzyme inhibitors. In some of these models, inflammatory mediators such as bradykinin and tachykinins have been shown to contribute to the enhanced coughing. While most of these studies have focussed on peripheral mechanisms, increases in central excitability of the cough reflex have been shown to occur as a result of airway inflammation. As such, we propose that enhanced coughing in pathological conditions is the result of plastic changes in both peripheral and central neural elements. Furthermore, we present a modified model of the neurogenesis of cough that takes into account peripheral and central plasticity induced by mediators of inflammation.

Animals↗

Sulfur-dioxide exposure increases TRPV1-mediated responses in nodose ganglia cells and augments cough in guinea pigs.

The objective of the present experiments was to study the effects of pulmonary inflammation induced by subacute Sulfur-dioxide (SO(2)) exposure on capsaicin-induced responses in isolated primary vagal sensory neurons and cough. Additionally, we examined the effects of SO(2) exposure on respiratory function and lung histology. All experiments were conducted 24 h after 4 days of subacute SO(2) (1000 ppm, 3 h/day for 4 days) exposure. In in vitro experiments, intracellular Ca(2+) concentrations were measured in single nodose ganglia cells isolated from SO(2) treated and control guinea pigs, using a fluorescence-based methodology. In nodose ganglia cells from SO(2)-exposed animals, intracellular Ca(2+) responses evoked by capsaicin (1 x 10(-7) and 1 x 10(-6) M) were significantly augmented (87% and 59%, respectively) compared to nodose ganglia from control animals. In vivo experiments, cough responses induced by a submaximal dose of aerosolized capsaicin (30 microM) were increased approximately 50% in SO(2) exposed animals compared to control animals. The enhanced cough response produced by SO(2) was inhibited by the corticosteroid, dexamethasone (10 mg/kg, p.o. b.i.d for 4 days and 10 mg/kg, p.o. once on day 5). In separate experiments, guinea pigs exposed to SO(2) displayed a decrease in respiratory frequency and minute ventilation and an increase in enhanced pause (PenH), a surrogate measure for pulmonary obstruction. Associated with the SO(2)-induced increase in cough and changes in respiratory parameters was an increase in BAL neutrophils. BAL neutrophil counts were 5+/-4 and 691+/-141 cells x 10(3)/ml for air and SO(2)-exposed animals, respectively. The neutrophillic inflammation induced by SO(2) was attenuated by dexamethasone treatment. Finally, staining for collagen, smooth muscle and goblet cells showed inflammation, remodeling and goblet cell metaphasia in the SO(2)-exposed animals. Our results demonstrate that SO(2) exposure enhances TRPV1 receptor function at the level of the nodose ganglia. This effect occurs in parallel with an increase sensitivity of the cough response to capsaicin.

Air Pollutants↗

Plasticity of peripheral mechanisms of cough.

The cough reflex pathway is characterized by a remarkable plasticity often resulting in a persistent and uncontrollable urge to cough during airway inflammation. In many instances cough becomes up regulated to the extent that ceases to fulfill its defensive role in protecting the airways. The exact mechanisms underlying this plasticity are unknown and likely involves a variety of factors influencing the function of the peripheral and central nervous system. This review outlines the evidence of increased cough sensitivity during airway disease. This is followed by a discussion of the peripheral mechanisms involved including the potential role of inflammatory mediators, neutrophins and changes in the airway mucosal structure. A greater understanding of the mechanisms leading to enhanced cough should lead to the development of more effective therapeutic strategies.

Animals↗

Plasticity of brainstem mechanisms of cough.

The cough reflex is a brainstem reflex, consisting of specific sensory afferent nerves which trigger the reflex, by transmitting the sensory input over vagal or laryngeal nerves to a brainstem circuitry which processes and ultimately transforms the sensory input into a complex motor output to generate cough. The first synaptic target for the primary cough-related sensory input is the second-order neurons in the nucleus tractus solitarius (NTS). This position in the reflex pathway and intricate local circuits within the nucleus make it a strategic site where the sensory information can be modified. Plasticity at this synapse will change the nature of the output--exaggerating it, suppressing it or transforming it into some other complex pattern. This review integrates evidence implicating the NTS in exaggerated cough with proof of the concept that NTS neurons undergo plasticity to contribute to an exaggeration of cough.

Afferent Pathways↗

Idiopathic chronic cough and organ-specific autoimmune diseases: a case-control study.

The marked female predominance in cases of idiopathic chronic cough and its association with mild chronic lymphocytic airway inflammation suggests an underlying autoimmune process. We set out to test the hypothesis that idiopathic chronic cough is associated with other organ-specific autoimmune diseases in a case control study. Twenty-two patients with idiopathic chronic cough and 65 community-matched controls for age and sex who responded to a self-administered questionnaire were asked about the presence of autoimmune disease, other medical problems and drug history. All subjects were invited to have a blood test for an autoimmune screen. Thirteen out of 22 (59%) patients with idiopathic chronic cough and eight out of 65 (12%) age- and sex-matched controls reported organ-specific autoimmune disease (odds ratio 8.8; 95% confidence interval 2.4-31.8, P<0.001). Organ-specific autoantibodies were present in a significantly higher proportion of cases than controls (40% vs. 13%; P = 0.047). These findings suggest a relationship between idiopathic chronic cough and organ-specific autoimmunity.

Adult↗

The role of proton pump inhibitors in the management of gastroesophageal reflux disease-related asthma and chronic cough.

Gastroesophageal reflux disease (GERD) occurs in at least one third of patients with asthma and is recognized as a potential trigger for asthma symptoms. The results of studies conducted in patients with both asthma and GERD, in which proton pump inhibitor (PPI) therapy is used to evaluate its effect on asthma outcome, are inconsistent, and many of these studies suffer from different design flaws. However, it does appear that PPI treatment may improve nocturnal asthma symptoms in patients who also have GERD. Moreover, both daytime asthmatic symptoms and pulmonary function seem to improve in some patients with PPI treatment. There is evidence that more severe GERD might predict a more favorable asthma outcome with PPI therapy. For effective management of GERD-related asthma, PPIs should be used at a dose double that of the standard dose for a minimum of 2 to 3 months. Although GERD is also known to be an important cause of chronic cough, there have been only 2 placebo-controlled trials investigating the efficacy of PPI on GERD-related chronic cough. Results of both of these trials suggest that PPI treatment relieves GERD-related chronic cough. As with GERD-related asthma, it would seem reasonable to use a double-standard dose of a PPI for a minimum of 2 to 3 months in the management of GERD-related chronic cough. However, larger, adequately planned studies are needed to confirm the role of PPIs in the management of GERD-related asthma and chronic cough.

Algorithms↗

Anesthesia for the superior laryngeal nerves and tartaric acid-induced cough.

OBJECTIVE: The internal branch of the superior laryngeal nerve (ibSLN) conveys impulses for the laryngeal cough reflex, which protects the laryngeal aditus and prevents the development of aspiration pneumonia. The purpose of this study was to determine the effect of bilateral anesthesia of the ibSLN on the cough reflex after inhalation of a nebulized chemoirritant solution of tartaric acid. DESIGN: Prospective, clinical investigation. SETTING: Outpatient. PARTICIPANTS: Nine healthy volunteers. INTERVENTIONS: Bilateral injections of 2% lidocaine solution without epinephrine into the paraglottic space containing the ibSLN. MAIN OUTCOME MEASURES: The tidal volume after inhalation of a nebulized 20% tartaric acid solution and forced vital capacity (FVC) were measured before and after injection. Data were analyzed using the Wilcoxon signed ranks, Mann-Whitney, and sign tests. RESULTS: Complete anesthesia of the ibSLN abolished the laryngeal cough reflex. Postinjection tidal volumes were significantly lower than preinjection volumes (p<.01). The decrease in tidal volumes for six subjects with complete bilateral anesthesia was significantly larger than the decrease in tidal volumes for three subjects with partial anesthesia (p<.05). FVC in both the six subjects with complete bilateral anesthesia and the three subjects with partial anesthesia did not significantly change from preinjection to postinjection. None of the subjects in this study had complications or adverse respiratory sequelae. CONCLUSION: Tartaric acid-induced cough may be useful in assessing the integrity of the laryngeal cough reflex after anesthesia or in patients with neurologic injury who are at risk of developing aspiration pneumonia. It may also be useful in making the decision whether to resume oral feeding.

Administration, Inhalation↗

Higher incidence of discontinuation of angiotensin converting enzyme inhibitors due to cough in black subjects.

OBJECTIVE: To compare the rates of discontinuation of angiotensin converting enzyme (ACE) inhibitors in patients with different racial and ethnic backgrounds. METHODS: A registry from a tertiary hypertension clinic consisting of 892 patients who received their first-ever dose of ACE inhibitor therapy was examined. Surveillance for cough was prospective, systematic, and constant beginning in 1986 and routinely included a trial of sinusitis therapy, followed by withdrawal and rechallenge before discontinuation of drug. RESULTS: The prevalence (per 100 patients) of cough requiring discontinuation of ACE inhibitor therapy was 62 of 644 (9.6 per 100) patients among black subjects compared with six of 248 (2.4 per 100) patients among others (odds ratio, 4.0; 95% confidence interval, 1.7 to 9.1; p < 0.001). There were no significant differences in discontinuation rates across the three most commonly used ACE inhibitors: captopril (6.6%; all black subjects), enalapril (6.1%; 94% black subjects), and lisinopril (7.3%; 90% black subjects). Cough was more common among women (70% of subjects). After adjustment (by backward stepwise multiple logistic regression analysis) for baseline differences, black subjects had a relative risk of 2.58 (95% confidence interval, 1.21 to 4.65; p = 0.01) of discontinuation of ACE inhibitor due to cough. CONCLUSIONS: These data suggest that there may be a race- or ethnicity-related difference in the prevalence of cough attributed to ACE inhibitor therapy. Although a race-related difference in ACE gene polymorphism has been suggested, further work is necessary to define the biological reason and pathophysiology for such a difference.

Angiotensin-Converting Enzyme Inhibitors↗

Antitussive effect of moguisteine on allergic coughs in the guinea pig.

The effect of moguisteine, a novel peripherally acting non-narcotic antitussive drug, on allergic coughs was examined in guinea pigs. Male Hartley guinea pigs were actively sensitized to ovalbumin. The number of coughs elicited over 5 min following a 2-min exposure to ovalbumin was counted. Exposure of sensitized guinea pigs to 0.5% ovalbumin aerosol induced 22.0 +/- 3.2 coughs/5 min. Moguisteine at doses of 30 and 56 mg/kg, p.o., dose-dependently and significantly suppressed the number of allergic coughs. Dihydrocodeine at doses of 30 and 56 mg/kg, p.o., dose-dependently but not significantly reduced the number of allergic coughs. These results suggest that moguisteine may be of a therapeutic benefit in reducing allergic coughs.

Analgesics, Opioid↗

Effects of moguisteine on the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve in guinea pigs.

The study aimed to further demonstrate the peripheral antitussive properties of moguisteine. Firstly, the antitussive effect of moguisteine on the cough reflex induced by inhalation of citric acid aerosol was evaluated in conscious guinea pigs. Secondly, the effects of both moguisteine and codeine on the centrally mediated cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve were investigated in anesthetized guinea pigs. Moguisteine (2.5-10 mg/kg, intravenously, i.v.) reduced the cough reflex induced by 7.5% citric acid aerosol in a dose-dependent manner, with an ED50 value of 0.55 mg/kg. Both i.v. (0.5-4 mg/kg) and intracerebroventricular (i.c.v., 5-20 microg) injection of codeine dose dependently inhibited the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve; the ED50 values were 0.91 mg/kg and 7.90 microg, respectively. The inhibitory effect of codeine (4 mg/kg i.v.) was abolished by pretreatment with naloxone (2 mg/kg intraperitoneally). In contrast to codeine, neither i.v. (4 and 20 mg/kg) nor i.c.v. (20 microg) injection of moguisteine affected the cough reflex. These results suggest that the antitussive effect of codeine is mediated by central opioid mechanisms, whereas the antitussive effect of moguisteine is mediated by peripheral mechanisms.

Aerosols↗

Assessment of the patient with chronic cough.

Chronic cough, defined as cough that persists for 3 weeks or longer, is one of the most common symptoms evaluated by a primary-care physician. With the exclusion of cigarette smoking, postnasal drip, asthma, and gastroesophageal reflux are responsible for more than 80% of the causes of chronic cough. Elicitation of a thorough history and performance of a physical examination will usually provide clues about the cause of chronic cough. The use of diagnostic tests including methacholine challenge, gastroesophageal reflux studies, and sinus imaging is based on clinical suspicion. Treatment of chronic cough is aimed at the underlying cause.

Asthma↗