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Treatment of chronic, refractory cough with baclofen.

Chronic, nonproductive cough may result from enhanced sensitivity of the cough reflex. Often, this debilitating symptom is refractory to standard antitussive therapy. Baclofen, an agonist of gamma-aminobutyric acid (GABA), has been shown, in animals, to have antitussive activity via a central mechanism. Recently, in normal subjects, we have demonstrated the ability of baclofen to inhibit capsaicin-induced cough, as well as cough due to angiotensin-converting enzyme (ACE) inhibitors. Herein, we describe two patients with chronic, refractory cough who obtained symptomatic improvement after a 14-day course of low-dose, oral baclofen, administered in a double-blind, placebo-controlled manner. In addition, both subjects demonstrated significant increases in cough threshold to inhaled capsaicin after treatment with baclofen.

Administration, Oral↗

Theophylline in the inhibition of angiotensin-converting enzyme inhibitor-induced cough.

Preliminary reports suggest that some pharmacologic agents may be effective in ameliorating angiotensin-converting enzyme (ACE) inhibitor-induced cough and, perhaps, allowing continuing use of ACE inhibitors in patients for whom this class of medication is important. We examined the effect of a once-a-day theophylline formulation on ACE inhibitor-induced cough and on the sensitivity of the cough reflex to capsaicin in 10 hypertensive patients who had developed cough during treatment with an ACE inhibitor. Theophylline did not induce bronchodilation but induced complete remission of clinical symptoms in 8 and attenuated the capsaicin-induced cough number in 7 subjects when compared with placebo. Theophylline may thus be effective in preventing ACE inhibitor-induced cough.

Adult↗

Effect of an NK1 receptor antagonist (CP-99,994) on hypertonic saline-induced bronchoconstriction and cough in male asthmatic subjects.

To investigate the role of NK1 receptors in the pathogenesis of bronchoconstriction and cough in asthma, we performed a randomized, double-blind, crossover study on the effects of a selective non-peptide tachykinin NK1 receptor antagonist (CP-99,994) on baseline measures of lung function and on hypertonic saline-induced bronchoconstriction and cough in 14 male subjects with mild asthma. CP-99,994 (250 micrograms/2 hours) and placebo were administered intravenously in 2-h infusions during consecutive visits 5 to 7 d apart. Specific airway resistance (SRaw) was measured and spirometry was performed at baseline and at 35 and 60 min. Next, hypertonic saline challenge was performed by delivering 10 breaths of saline of increasing concentration (0.9 to 7% in 1% increments at 5-min intervals) via an ultrasonic nebulizer until SRaw increased from baseline by 200% or 20 units, whichever was greater. Throughout the challenge cough was counted from a taped record made from two microphones placed close to the subject's larynx. We found that CP-99,994 did not significantly affect SRaw or spirometric measures of lung function during the first hour of infusion. Although CP-99,994 infusion markedly attenuated the bronchoconstrictor response to the saline challenge in two subjects, it did not significantly decrease the area under curves obtained for SRaw and cough during saline challenge for the group as a whole (p = 0.9 for SRaw;p = 0.8 for cough). We conclude that administration of 250 micrograms/kg of CP-99,994 over 2 h does not significantly inhibit hypertonic saline-induced bronchoconstriction or cough in subjects with mild asthma and does not have acute bronchodilator activity in these subjects.

Adult↗

Defective motor control of coughing in Parkinson's disease.

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.

Abdominal Muscles↗

Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.

A successful, systematic, anatomic, diagnostic protocol for evaluating patients with chronic cough was presented in 1981. To determine whether it was still valid, we prospectively evaluated, over a 22-month interval, 102 consecutive and unselected immunocompetent patients complaining of cough an average of 53 +/- 97 months (range, 3 wk to 50 yr). Utilizing the anatomic, diagnostic protocol modified to include prolonged esophageal pH monitoring (EPM), the causes of cough were determined in 101 of 102 (99%) patients, leading to specific therapy that was successful in 98%. Cough was due to one condition in 73%, two in 23%, and three in 3%. Postnasal drip syndrome was a cause 41% of the time, asthma 24%, gastroesophageal reflux (GER) 21%, chronic bronchitis 5%, bronchiectasis 4%, and miscellaneous conditions 5%. Cough was the sole presenting manifestation of asthma and GER 28 and 43% of the time, respectively. While history, physical examination, methacholine inhalational challenge (MIC), and EPM yielded the most frequent true positive results, MIC was falsely positive 22% of the time in predicting that asthma was the cause of cough. Laboratory testing was particularly useful in ruling out suspected possibilities. We conclude that the anatomic diagnostic protocol is still valid and that it has well-defined strengths and limitations.

Adolescent↗

Chronic cough: bronchoscopy or pulmonary function testing?

To determine how frequently bronchoscopic examination and pulmonary function testing are useful in establishing a diagnosis in patients with chronic cough as an isolated clinical symptom, we reviewed the records of all patients referred to pulmonary specialists at 3 community hospitals for evaluation of cough over a 6-yr period. There were 109 patients with the isolated symptom of chronic cough and a normal or stable chest roentgenogram. Bronchoscopy was performed in 51. All patients but 1 were followed until the cough disappeared or for a minimum of 1 yr. Carcinoma was established as the cause for cough in 1 patient. Spirometry and/or bronchial inhalation challenge was performed in 87 patients. Previously undiagnosed asthma was discovered in 39 patients by these means. Pulmonary function testing has diagnostic value in this population, but bronchoscopy is of limited value in determining the cause of isolated chronic cough.

Adolescent↗

Chronic cough as a sign of laryngeal sensory neuropathy: diagnosis and treatment.

Chronic cough is often attributed to reflux, postnasal drip, or asthma. We present 28 patients who had chronic cough or throat-clearing as a manifestation of sensory neuropathy involving the superior or recurrent laryngeal nerve. They had been identified as having sudden-onset cough, laryngospasm, or throat-clearing after viral illness, surgery, or an unknown trigger. Cough and laryngospasm were the most common complaints. Seventy-one percent of the patients had concomitant superior laryngeal nerve or recurrent laryngeal nerve motor neuropathy documented by laryngeal electromyography or videostroboscopy. After a negative workup for reflux, asthma, or postnasal drip, these patients were treated with gabapentin at 100 to 900 mg/d. Symptomatic relief was achieved in 68% of the patients. Sensory neuropathy of the recurrent laryngeal nerve or superior laryngeal nerve should be considered in the workup for chronic cough or larynx irritability. Symptomatic management of patients with cough and laryngospasm due to a suspected sensory neuropathy may include the use of antiseizure medications such as gabapentin.

Adolescent↗

Primary tracheomalacia and gastroesophageal reflux in infants with cough.

Cough is an uncommon sign in infants. Cough may result from the presence of abnormal secretions in the airway or abnormalities of the central airways that affect the infant's ability to clear normal secretions. Tracheomalacia (TM) and gastroesophageal reflux (GER) can both cause cough in infants. Four infants whose cough began in the newborn period were diagnosed with TM and GER. Symptoms of central airway obstruction (homophonous wheeze or tracheal cough) suggested the diagnoses. In three patients, the diagnosis was made by barium esophagraphy and airway fluoroscopy. The infants responded to conservative and medical therapy for GER and to nebulized bronchodilators. Tracheomalacia and GER cause cough in infants that begins in the newborn period. The diagnosis can often be made with studies available to the primary care provider, and the conditions are often responsive to medical management.

Aerosols↗

Efficacy of fluticasone on cough: a randomised controlled trial.

Cough may be the consequence of bronchial hyperresponsiveness (BHR) and inflammation. This study was designed to investigate the short-term effects of an inhaled steroid (fluticasone propionate (FP)) on cough, and to determine the effects of smoking, BHR, allergy and forced expiratory volume in one second (FEV1) on the efficacy of FP. In a community-based primary healthcare centre, 135 previously healthy adults suffering from cough for > or =2 weeks were enrolled in a randomised, double-blind, placebo-controlled trial of inhaled FP 500 microg b.i.d. for 2 weeks. Participants completed daily diary cards of lower respiratory tract symptoms. The primary outcome measure was the decrease in mean total daily cough score (0-6) during the second week of treatment. In the FP group, the cough score decreased from 3.8 at baseline to mean+/-SEM 1.4+/-0.2 during the second week. In the placebo group, this decrease was from 3.8 to 1.9+/-0.1 and was statistically significantly less. A favourable effect of FP was only detectable in nonsmokers, in whom the score was 0.9 points lower compared with placebo. The clinical relevance of this finding has to be established further. Allergy, FEV1 and BHR at baseline did not affect the efficacy of FP. In conclusion, anti-inflammatory treatment with the inhaled steroid fluticasone propionate reduces cough in otherwise healthy adults who do not smoke.

Administration, Inhalation↗

Effect of smoking cessation on cough reflex sensitivity.

Recent studies have shown that cigarette smokers have diminished cough reflex sensitivity compared with nonsmokers. The current authors proposed a mechanism of chronic cigarette smoke-induced desensitisation of airway cough receptors. To investigate this hypothesis, cough sensitivity to inhaled capsaicin (C5) in chronic smokers was measured both while they were actively smoking and 2, 6, 12 and 24 weeks after smoking cessation. In total, 29 subjects underwent baseline capsaicin challenge while smoking and 2 weeks after smoking cessation. Mean+/-sem log C5 fell from 1.86+/-0.12 to 1.60+/-0.12, demonstrating significant enhancement of cough reflex sensitivity. Of the total, 20, 18 and 14 subjects successfully abstained from smoking for 6, 12 and 24 weeks, respectively. Mean log C5 values after 12 and 24 weeks of smoking cessation were significantly diminished from baseline. In a control group of smokers, mean log C5 did not decrease from baseline after 6, 12 and 24 weeks. Overall, the log C5 profile of the smoking cessation group showed a clear, linearly decreasing trend over time compared with the control group. Even after many years of smoking, cough sensitivity is enhanced as early as 2 weeks after smoking cessation. Given the importance of an intact cough reflex, these changes may provide clinical benefit.

Adult↗

Cough: what's in a name?

The cough reflex (CR) and the expiration reflex (ER) are two defensive reflexes from the respiratory tract, the latter mainly from the larynx. Both are elicited by mechanical and chemical irritation of the airway mucosa, and are a characteristic of airway diseases, but they have different functions. The CR first draws air into the lungs, to accentuate the subsequent expulsive phase; the ER consists of a strong expiration, to prevent aspiration of material into the lungs. They have different sensory pathways, central nervous circuits, and physiological and pharmacological modulations. In practice, coughing often consists of a combination of the two reflexes, a cough bout, epoch or attack. Articles on cough usually do not distinguish between the two reflexes, or whether the coughs are single events or epochs; they usually only measure frequency of expiratory efforts, and neglect other aspects. Current methods for measuring and assessing cough are described, with indications of when the use of these methods may be important.

Bronchi↗

Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young females.

We have shown previously that female sex is a determinant of cough sensitivity to inhaled capsaicin, but the relationship between atopy and the cough sensitivity has not been examined. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, nonspecific bronchial responsiveness, defined as the provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (PC20), total immunoglobulin E (IgE) and specific IgEs to eight common aeroallergens (house dust 1, 2 and 6, Dermatophagoides pteronyssinus and D. farinae, Japanese cedar, ragweed and orchard grass) in the serum were measured in 71 nonsmoking, healthy young women aged 20.6+/-0.1 yrs (mean+/-EM). A structured interviewer-led questionnaire on allergic diseases revealed that one and six subjects had mild current and past asthma, respectively. These seven subjects were excluded from the data analysis. PC20 was significantly lower in 42 subjects showing a positive specific IgE than in 22 subjects showing a negative specific IgE to any of the eight allergens (p<0.05), while the capsaicin cough threshold was not significantly different between the subgroups. PC20 was significantly lower in subjects with positive specific IgE to Dermatophagoides and house dust, but not to the three kinds of pollen examined. It was confirmed that atopy indicated by specific immunoglobulin E to mite-related antigens, but not to pollen antigens, is associated with nonspecific bronchial responsiveness, and it is suggested that atopy is not a determinant of airway cough sensitivity in healthy, nonasthmatic subjects.

Adult↗

Bronchoalveolar lavage findings in patients with chronic nonproductive cough.

Mast cells and eosinophils may play a role in the pathophysiology of chronic cough in nonasthmatics. It is unknown, however, whether degranulation of these cells occurs in the airways of such patients. Thirty-five nonsmoking patients referred with a chronic nonproductive cough (mean cough duration 76.2 months) were evaluated using a comprehensive diagnostic protocol. Bronchoalveolar lavage (BAL) cell differentials and BAL histamine, tryptase and eosinophilic cationic protein (ECP) concentrations were determined. Ten nonsmoking healthy volunteers served as controls. Diagnostic subgroups were identified: eight postnasal drip syndrome (PNDS), seven cough variant asthma (CVA), seven gastro-esophageal reflux (GOR), seven dual aetiology and six idiopathic. Nonasthmatic coughers (NAC) were characterized as those patients without bronchial hyperresponsiveness on histamine challenge and whose cough had either responded to therapy for PNDS or GOR or failed to improve with antiasthma therapy. There was a significant increase in both eosinophil and mast cell numbers (p<0.05) and in histamine levels (p = 0.027) when NAC patients were compared with controls. Tryptase and ECP levels were elevated in 7 of 23 and 6 of 23 NAC patients, respectively. In conclusion, airway inflammatory cell numbers are not only increased but also activated, suggesting an important role for airways inflammation in the pathophysiology of chronic nonproductive cough.

Adult↗

Health seeking behaviour, health system experience and tuberculosis case finding in Gambians with cough.

BACKGROUND: Studies in Africa investigating health-seeking behaviour by interviewing tuberculosis patients have revealed patient knowledge issues and significant delays to diagnosis. We aimed to study health-seeking behaviour and experience of those with cough in The Gambia and to identify whether they had tuberculosis. METHODS: During a round of a population under 3-monthly demographic surveillance, we identified people >10 years old who had been coughing > or = 3 weeks. A questionnaire was administered concerning demographic data, cough, knowledge, health seeking, and experience at health facilities. Case finding utilised sputum smear and chest X-ray. RESULTS: 122/29,871 coughing individuals were identified. Of 115 interviewed, 93 (81%) had sought treatment; 76 (81.7%) from the health system. Those that visited an alternative health provider first were significantly older than those who visited the health system first (p = 0.03). The median time to seek treatment was 2 weeks (range 0-106). 54 (58.1%) made their choice of provider because they believed it was right. Of those who left the health system to an alternative provider (n = 13): 7 believed it was the best place, 3 cited cost and 2 failure to improve. 3 cases were identified by sputum analysis, 11 more by X-ray; all had visited the health system first. Total 'excess' cough time was 1079 person weeks. CONCLUSION: The majority of people with cough in this population seek appropriate help early. Improved case detection might be achieved through the use of chest X-ray in addition to sputum smear.

Adolescent↗

Benzonatate for opioid-resistant cough in advanced cancer.

Chronic cough is a distressing symptom experienced by approximately 37% of patients with advanced cancer. Palliation of chronic nonproductive cough should always first address the underlying cause but in some patients chronic, nonproductive cough persists and antitussive agents are required. Opioids are the gold standard cough suppressants, of which codeine is the most widely used; patients with an opioid-resistant cough often prove to be a therapeutic challenge. We report three patients with an opioid-resistant cough who achieved symptomatic relief with the peripherally acting nonopioid drug benzonatate.

Adenocarcinoma↗

Cough, exertional, and sexual headaches: an analysis of 72 benign and symptomatic cases.

We analyzed our experience with cough, exertional, and vascular sexual headaches, evaluated the interrelationships among them, and examined the possible symptomatic cases. Seventy-two patients consulted us because of headaches precipitated by coughing (n = 30), physical exercise (n = 28), or sexual excitement (n = 14). Thirty (42%) were symptomatic. The 17 cases of symptomatic cough headache were secondary to Chiari type I malformation, while the majority of cases of symptomatic exertional headaches and the only case of symptomatic sexual headache were secondary to subarachnoid hemorrhage. Although the precipitant was the same, benign and symptomatic headaches differed in several clinical aspects, such as age at onset, associated clinical manifestations, or response to pharmacologic treatment. Although sharing some properties, such as male predominance, benign cough headache and benign exertional headache are clinically separate conditions. Benign cough headache began significantly later, 43 years on average, than benign exertional headache. By contrast, our findings suggest that there is a close relationship between benign exertional headache and benign vascular sexual headache. We conclude that benign and symptomatic cough headaches are different from both benign and symptomatic exertional and sexual headaches.

Adolescent↗

Intravenous lidocaine suppresses fentanyl-induced coughing: a double-blind, prospective, randomized placebo-controlled study.

IV lidocaine is effective in suppressing the cough reflex of tracheal intubation, extubation, bronchography, bronchoscopy, and laryngoscopy. We investigated this effect of lidocaine on fentanyl-induced cough in 502 patients of ASA physical status I and II scheduled for elective surgery. The patients were assigned to 2 equal groups to receive either lidocaine 1.5 mg/kg or placebo (0.9% saline) over 5 s 1 min before the administration of fentanyl 3 mug/kg in a randomized and double-blind fashion. Coughs were classified as coughing and graded as mild (1-2), moderate (3-4), or severe (5 or more). The results of the study suggest that IV lidocaine 1.5 mg/kg, when administered 1 min before fentanyl, is significantly effective in suppressing fentanyl-induced cough compared to placebo (0.9% saline) (218 versus 165 patients) (P < 0.002) but without affecting the severity of cough (P > 0.05).

Adult↗

Prolonged injection time and light smoking decrease the incidence of fentanyl-induced cough.

We designed this study to evaluate the effect of injection time and smoking on fentanyl-induced cough. Four-hundred-fifty ASA class I-II patients, aged 18-80 yr and weighing 40-90 kg, scheduled for elective surgery were included. All patients received fentanyl (100 microg for patients weighing 40-69 kg and 150 microg for patients weighing 70-90 kg for clinical convenience) via the proximal port of a peripheral IV line on the forearm. Patients were randomly assigned to 3 groups of 150 patients each. Patients in Group I received fentanyl injection over 2 s, whereas for patients in Groups II and III the fentanyl was injected at a constant rate over 15 s and 30 s, respectively. We recorded the number of coughs of each patient during and 30 s after fentanyl injection. The incidence of cough was 18% in group I, 8% in Group II, and 1.3% in Group III, significantly less (P < 0.05) with a longer injection time. Current smokers had a less frequent incidence of cough than nonsmokers; however, this effect was only significant in light smokers (<10 cigarettes per day or <10 smoking years or <10 pack-years). In conclusion, a longer injection time reduces the incidence of fentanyl-induced cough, and light smoking may be a protective factor against fentanyl-induced cough.

Adolescent↗