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PubMed1994

ACE inhibitors and cough.

Probably the most common and irritating side effect of angiotensin-converting enzyme (ACE) inhibitors is cough. In this retrospective study the incidence of cough was investigated in 1113 patients with arterial hypertension who were receiving ACE inhibitors alone or in combination with other antihypertensive agents. Patients were treated with one of the following ACE inhibitors: enalapril 10-20 mg/day (n:668), captopril 25-75 mg/day (n:234), perindopril 2-8 mg/day (n:90), or lisinopril 5-20 mg/day (n:121). Mean follow-up periods were twenty-six months with enalapril, twenty-nine months with captopril, eleven months with perindopril, and thirteen months with lisinopril. Spontaneously declared cough incidence in enalapril, captopril, perindopril, and lisinopril groups were 7%, 5.1%, 2.2%, and 1.6%, respectively. Cough was not dose related. Treatment was stopped in all patients with cough. In 59% of patients the onset of cough occurred after the first month of treatment (thirty to one hundred eighty days). Cough decreased by 50% within three days of drug cessation and disappeared in ten days. Mean age of patients with cough was 58.7 years and 79% of them were women. In patients without cough, mean age was 57.8 years and 56% of them were women. There was no significant difference between the two groups regarding mean age, but the sex difference between groups was statistically significant (P < 0.05). In conclusion, although cough may occur with all four types of ACE inhibitors, the incidence of this side effect was higher during enalapril and captopril treatment than during lisinopril and perindopril treatment. The incidence was also greater in women than in men.

Adult↗
PubMed1991

Characterization of cough associated with angiotensin-converting enzyme inhibitors.

Chronic cough is a side effect of the angiotensin-converting enzyme (ACE) inhibitor class of antihypertensives. The cough is thought to be a result of inhibition of the enzymes that break down some of the mediators of inflammation, such as the bradykinins and tachykinins. We report 20 patients with chronic cough caused by ACE inhibitors and some of the characteristics of the cough. The cough is typically dry, nonproductive, and worse at night. Interference with sleep is common and was severe in three patients. Women outnumbered men in this series: urinary stress incontinence developed in five, rectal and vaginal prolapse developed in one. Three patients felt they were incapacitated by the cough. Most had been on multiple medications; only oxycodone was reported to be effective in controlling the cough, and four patients thought they were addicted to that. All coughs resolved with withdrawal of the ACE inhibitor. Chronic cough is common among individuals taking ACE inhibitors. It may be severe and associated with complications. The incidence and potential severity is understated in drug information sources, and patients and physicians often fail to recognize cough as a drug side effect.

Adult↗
PubMedDate not supplied

A phase II study of hydrocodone for cough in advanced cancer.

PURPOSE: Cough is a common symptom in advanced cancer. The use of hydrocodone as an antitussive has not been studied previously in this setting. This study evaluates hydrocodone for cough in advanced cancer METHODS: The results presented are from a phase II study with dose titration. SETTING: Palliative medicine program in a tertiary referral center PATIENTS: 25 consecutive patients with cough from irreversible causes, on a stable opioid regimen for the prior 24 hours, and no previous or current use of hydrocodone for cough. INTERVENTION: 5 mg hydrocodone was administered twice daily. The dose was then titrated daily (maximum: 60 mg/24 h), if needed, until a > or = 50 percent improvement of the frequency of cough was achieved and then maintained for three consecutive days. MEASUREMENTS: Cough severity, frequency, complications, and hydrocodone side effects. RESULTS: 20 persons (10 women and 10 men) completed study evaluation. Median age was 63 years (range: 42-82). Nine patients had lung cancer and seven had lung or pleura metastases; 19 patients had at least 50 percent improvement of their cough frequency. The median best response was 70 percent improvement in the cough frequency (range: 50-90 percent). Median hydrocodone dose associated with the best response was 10 mg/day (range: 5-30 mg/day). Cough severity, frequency, associated symptoms and complications, and activities of daily living improved significantly. Side effects of hydrocodone (dry mouth, nausea, and drowsiness) were tolerable and rated as mild. CONCLUSIONS: Hydrocodone is effective and safe to treat cough in advanced cancer A starting dose of 10 mg per day in divided doses seems effective. Dose escalation may be required. Most improved within one day.

Adult↗
PubMed1995

Objective assessment of cough.

Cough is a primitive reflex typically consisting of an initiating deep inspiration, glottal closure, and an explosive expiration accompanied by a sound. The flow characteristics of cough have been shown to differ between different pulmonary diseases. Cough sounds are generated at the larynx and in the lungs. Modern analysing techniques have also been applied in cough sound studies, and differences in cough sound duration and spectra have been found in pulmonary diseases with different bronchopulmonary pathophysiology. Since the objective assessment of cough is clinically important, automatic cough detectors and counters have been constructed, e.g. to assess the efficacy of antitussive drugs. Also, ambulatory methods for assessment of cough have been reported. This review includes a brief history of cough research and present methods available for objective assessment of cough.

Bronchi↗
PubMed1996

Night cough in a population-based sample of children: characteristics, relation to symptoms and associations with measures of asthma severity.

Nocturnal cough in asthma is a common but poorly understood phenomenon. The aims of this study were to determine the relationship between recorded night cough, reported night cough and current wheeze in a population-based sample of children previously identified as wheezy, and to examine the relationship of nocturnal cough to current symptoms, markers of asthma severity and environmental exposure. Children were reassessed in the early school years by measuring current symptoms, ventilatory function, bronchial reactivity, peak flow variability, respiratory symptom diaries and home monitoring of overnight cough, transcutaneous arterial oxygen saturation, room temperature and humidity. Night studies were performed on 59 asymptomatic children and 41 children with current wheeze. Cough occurred more frequently in current wheezers compared to asymptomatic children (16 out of 41 (39%) vs 11 out of 59 (19%)), and more cough episodes were recorded (median 3.5 vs 2.0). Night cough was not associated with bronchial reactivity, peak flow variability, degree of morning dip, mean overnight arterial oxygen saturation, ventilatory function, maternal smoking or treatment of asthma. However, it was associated with lower overnight air temperature. Although night cough is more common in current wheezers, there is poor agreement between recorded and reported night cough. Objective tests of asthma severity are of little use in predicting its presence in this age group. The sleeping environment deserves further study.

Asthma↗
PubMed2000

Antitussive efficacy of dextromethorphan in cough associated with acute upper respiratory tract infection.

Dextromethorphan is one of the most widely used antitussives for the treatment of cough associated with acute upper respiratory tract infection. However, there is very little data to support the efficacy of dextromethorphan in this disease state. This aim of this study was to obtain more information about the efficacy of a single dose of 30 mg dextromethorphan in the treatment of cough associated with acute upper respiratory tract infection. The study was a double-blind, stratified, randomized and parallel group design. Both objective and subjective measurements of cough were recorded over 10-min recording periods in a quiet room before (baseline) and at 90, 135 and 180 min after treatment. Forty-three patients (30 females and 13 males), mean age 22.9 years (range 18-46 years), with acute dry or slightly productive cough and otherwise healthy were included in the study. Patients were randomized to placebo treatment (n = 22) and dextromethorphan treatment (n=21). The results showed similar trends in both treatment groups with statistically significant reductions (P < 0.05) in cough sound pressure level (CSPL), cough frequency (CF) and subjective scores for cough severity within treatment groups but little difference between the treatment groups during the study period. The only statistically significant difference between treatment groups was for the mean CSPL changes from baseline to 90 min (P=0.019). There was a significant positive correlation between CSPL and CF (r = 0.752, P= 0.000) for changes in cough measurements from baseline to 90 min after treatment and this indicates that CSPL may be a useful measure of cough severity. This study provides very little if any support for clinically significant antitussive activity of a single 30 mg dose of dextromethorphan in patients with cough associated with acute upper respiratory tract infection.

Adolescent↗
PubMed1993

Intravenous lidocaine as a suppressant of coughing during tracheal intubation in elderly patients.

The effects of intravenously administered lidocaine on cough suppression in elderly patients over the age of 60 yr during tracheal intubation under general anesthesia were evaluated in two studies. In the first study, 100 patients received a placebo of either 0.5, 1.0, 1.5, or 2.0 mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1.5 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P < 0.01). In the second study, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in Study 1. The incidence of coughing decreased significantly (P < 0.01) when 2 mg/kg lidocaine was injected intravenously between 1 min and 3 min before attempting intubation. The cough reflex was almost entirely suppressed by plasma concentrations of lidocaine in excess of 4 micrograms/mL. The results suggest that intravenous administration of lidocaine is effective in suppressing the cough reflex during tracheal intubation in elderly patients under general anesthesia, but that relatively high plasma concentrations of lidocaine may be required for suppression of coughing.

Aged↗
PubMed1986

Chronic cough in infants and children.

Chronic cough is an important, sometimes frustrating problem, often encountered by the otolaryngologist-head and neck surgeon. Thirty-eight infants and children under age 16 with a normal chest roentgenogram were evaluated for chronic cough persisting for longer than 4 weeks. Specific therapy (rather than symptomatic treatment) of chronic cough lead to a resolution or control of the cough in 33 (87%). Cough-variant asthma was by far the most common cause of chronic cough, followed by sinusitis, aberrant innominate artery, psychogenic cough, and subglottic stenosis. In addition to a detailed history, physical examination, and chest roentgenogram, endoscopy, paranasal sinus roentgenograms, and pulmonary function studies with methacholine challenge testing were particularly effective for establishing a precise diagnosis. Chronic cough is best managed by determining the precise cause of the cough, then specifically treating the underlying disorder. Children with persistent cough and a normal chest roentgenogram should be referred promptly for evaluation by an otolaryngologist when the primary physician's initial efforts at diagnosis and treatment are unsuccessful. Endoscopy is under-utilized in practice and its importance is understated in the literature. It is particularly helpful in establishing a precise diagnosis in infants under 18 months of age.

Adolescent↗
PubMed1991

Chronic cough in infants and children: an update.

Cough is a symptom frequently encountered by the otolaryngologist--head and neck surgeon. Although most coughs are self limited, chronic cough often proves to be a frustrating problem. Seventy-two infants and children under age 16 with a normal chest radiogram have now been evaluated for chronic cough persisting for longer than 4 weeks. Cough-variant asthma was the most common cause of cough, followed by sinusitis, gastroesophageal reflux, aberrant innominate artery, psychogenic cough, and subglottic stenosis. Chronic cough is best managed by first following an individualized diagnostic protocol designed to determine the etiology of the cough. This is followed by specific therapy to treat the underlying disorder. Children with persistent cough and normal chest radiograph are best served when referred promptly for evaluation by an otolaryngologist when the primary physician's initial efforts at diagnosis and treatment are not effective. Endoscopy is underutilized in practice and its importance understated in the literature. It is particularly helpful in establishing a precise diagnosis in infants under 18 months of age.

Adolescent↗
PubMed1993

Functional electrical stimulation to enhance cough in quadriplegia.

Respiratory problems are a major cause of death in the acute and chronic phases of cervical spinal cord injury (CSCI); CSCI paralyzes the intercostal and abdominal muscles, reducing ability to cough and clear secretions. Impaired cough due to neuromuscular disorders can be assessed with the maximum expiratory pressure (MEP). This study consists of two experiments with CSCI patients. In the first, MEP measurements were recorded with the following maneuvers performed: (1) spontaneous cough attempts, (2) manually assisted cough, and (3) cough attempts with functional electrical stimulation (FES) applied to the abdominal wall. In the second, spontaneous cough attempts and cough attempts with a portable FES unit were recorded. These CSCI patients were found to have a greatly reduced MEP when they coughed spontaneously. Either FES-assisted or manually assisted coughing increased the MEP in all patients studied. By increasing the MEP, abdominal muscle FES could enhance cough in quadriplegics.

Abdominal Muscles↗
PubMed2002

Evaluation of a cough-specific quality-of-life questionnaire.

STUDY OBJECTIVE: To psychometrically evaluate a cough-specific quality-of-life questionnaire (CQLQ) in adults. DESIGN: Prospective evaluation of CQLQ using three different cohorts of adult subjects with cough. SETTING: Academic tertiary-care ambulatory medical facilities. PARTICIPANTS: One hundred fifty-four subjects complaining of chronic cough, 30 of acute cough, and 31 smokers with cough. INTERVENTIONS: Self-administration of the CQLQ in acute coughers, smokers, and chronic coughers before and after therapy. MEASUREMENTS: Psychometric analyses including factor analysis (FA), and assessments of reliability and validity. RESULTS: Acute and chronic cough data were subjected to FA, and the Cronbach alpha and interitem correlations were computed. FA of chronic and acute cough data (n = 184) revealed six subscales. The Cronbach alpha for the total CQLQ was 0.92, and it was 0.62 to 0.86 (mean, 0.76) for the six subscales. Interitem correlations for the total CQLQ ranged from -0.06 to 0.72, with a mean of 0.28. Test-retest reliability in 52 chronic coughers demonstrated nonsignificant changes with readministration of the questionnaire, and the intraclass correlation for total CQLQ was 0.89, and for the subscales the range was 0.75 to 0.93. Analysis of variance followed by tests of contrasts among all possible pairings of chronic coughers, acute coughers, and smokers showed significant differences (p < or = 0.001) among the groups. Posttreatment cure scores were significantly lower (p < or = 0.001) than pretreatment scores in 24 chronic coughers. CONCLUSIONS: The 28-item CQLQ has dimensionality that is consistent with a cough-specific quality-of-life instrument. It is a valid and reliable method by which to assess the impact of cough on the quality of life of chronic and acute coughers, and the efficacy of cough therapies in chronic coughers.

Activities of Daily Living↗
PubMed2003

Chronic cough and gastroesophageal reflux disease: experience with specific therapy for diagnosis and treatment.

STUDY OBJECTIVE: To evaluate experience using a therapeutic trial of proton-pump inhibitor therapy with or without a prokinetic agent in diagnosis and treatment of gastroesophageal reflux disease (GERD)-related cough. DESIGN: A review of experience with 214 patients with cough of > or = 3 weeks referred over 3.5 years. An anatomic diagnostic protocol was used to identify and treat those with GERD-related cough. SETTING: A pulmonary specialty practice affiliated with the University of Rochester School of Medicine and Dentistry. PATIENTS: One hundred eighty-three patients were identified with chronic cough and were included in the study. Thirty-one patients were disqualified because of abnormal chest radiographic findings, inadequate follow-up, or cough being not the primary complaint. Fifty-six patients were identified as having GERD-related cough. INTERVENTIONS: A once-daily dose of a proton-pump inhibitor was prescribed. A prokinetic agent was added if esophageal dysfunction was suspected or response was inadequate. Those who did not respond underwent 24-h esophageal pH monitoring. RESULTS: GERD was the single cause of cough in 24 patients (43%). Twenty-nine patients (52%) had GERD plus another cause, and 3 patients (5%) had GERD with more than two causes. Twenty-four patients (43%) had cough only, while 32 patients (57%) had other symptoms of GERD. Proton-pump therapy was successful in 42 patients (79%). Twenty-four patients responded to proton-pump inhibitor therapy, and 18 patients responded when metoclopramide or cisapride was added. The remaining two patients responded to a histamine type-2 blocker or cisapride alone. The cough was eliminated or markedly improved in 38 patients (86%) after 4 weeks and by 8 weeks in the remaining 6 patients. Six of the nonresponders had aspiration diagnosed by bronchoscopy. Four patients had fundoplication recommended, and two patients responded to alternative interventions. CONCLUSIONS: Four to 6 weeks of a proton-pump inhibitor alone or in combination with a prokinetic agent successfully diagnoses and treats four of five patients with GERD-related cough. Twenty-four-hour esophageal pH monitoring will confirm the diagnosis in the others. These patients may be candidates for fundoplication. Nonresponders often aspirate as an additional aggravating factor.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Effect of guaifenesin on cough reflex sensitivity.

BACKGROUND: Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. STUDY OBJECTIVES: To evaluate the effect of guaifenesin on cough reflex sensitivity. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Academic medical center. PARTICIPANTS: Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. INTERVENTIONS: On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. MEASUREMENTS AND RESULTS: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. CONCLUSIONS: Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Adult↗
PubMed2006

Uncommon causes of cough: ACCP evidence-based clinical practice guidelines.

OBJECTIVES: To describe the uncommon causes of cough. DESIGN/METHODOLOGY: An English language literature search by MEDLINE citations from 1975 through 2004 was used to identify publications on uncommon pulmonary and nonpulmonary disorders in which cough was present as the major or presenting symptom in >50% of those persons affected by the uncommon diseases. RESULTS: A substantial number of uncommon or rare pulmonary and nonpulmonary disorders were identified. The uncommon occurrence of these diseases made it difficult to develop a meaningful evidence-based guideline to the diagnosis and therapy of many of the uncommon causes of cough. As cough was the major or presenting symptom, it was usually initially attributed to common respiratory diseases (eg, asthma or bronchitis). As a result, a substantial time lag existed from the onset of cough to the diagnosis of the etiologic entity. Diagnostic tests limited to the respiratory system did not always provide clues to the diagnosis of uncommon causes of cough. CONCLUSIONS: Cough is the major or presenting symptom in many uncommon pulmonary and nonpulmonary disorders. A strong index of suspicion is essential to consider and diagnose the uncommon causes of cough. The diagnosis and management of cough in patients with uncommon causes of cough is dependent on the underlying etiology.

Connective Tissue Diseases↗
PubMed2006

An empiric integrative approach to the management of cough: ACCP evidence-based clinical practice guidelines.

OBJECTIVE: Review the literature to provide a comprehensive approach, including algorithms for the clinician to follow in evaluating and treating the patient with acute, subacute, and chronic cough. METHODS: We searched MEDLINE (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms "cough," "treatment of cough," and "empiric treatment of cough." We selected case series and prospective descriptive clinical trials. We also obtained any references from these studies that were pertinent to the topic. RESULTS: The relative frequency of the disorders (alone and in combination) that can cause cough as well as the sensitivity and specificity of many but not all diagnostic tests in predicting the cause of cough are known. An effective approach to successfully manage chronic cough is to sequentially evaluate and treat for the common causes of cough using a combination of selected diagnostic tests and empiric therapy. Sequential and additive therapy is often crucial because more than one cause of cough is frequently present. CONCLUSION: Algorithms that provide a "road map" that the clinician can follow are useful and are presented for acute, subacute, and chronic cough.

Algorithms↗
PubMed2006

Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines.

BACKGROUND: Cough-suppressant therapy, previously termed nonspecific antitussive therapy, incorporates the use of pharmacologic agents with mucolytic effects and/or inhibitory effects on the cough reflex itself. The intent of this type of therapy is to reduce the frequency and/or intensity of coughing on a short-term basis. METHODS: Data for this review were obtained from several National Library of Medicine (PubMed) searches (from 1960 to 2004), which were performed between May and September 2004, of the literature published in the English language, limited to human studies, using combinations of the search terms "cough," "double-blind placebo-controlled," "antitussive," "mucolytic," "cough clearance," "common cold," "protussive," "guaifenesin," "glycerol," and "zinc." RESULTS: Mucolytic agents are not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Peripheral and central antitussive agents can be useful in patients with chronic bronchitis, but can have little efficacy in patients with cough due to upper respiratory infection. Some protussive agents are effective in increasing cough clearance, but their long-term effectiveness has not been established. DNase is not effective as a protussive agent in patients with cystic fibrosis. Inhaled mannitol is acutely effective in this patient population, but its therapeutic potential must be investigated further. CONCLUSIONS: These findings suggest that suppressant therapy is most effective when used for the short-term reduction of coughing. Relatively few drugs are effective as cough suppressants.

Antitussive Agents↗
PubMed2006

Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines.

OBJECTIVES: To critically review and summarize the literature on cough and gastroesophageal reflux disease (GERD), and to make evidence-based recommendations regarding the diagnosis and treatment of chronic cough due to GERD. DESIGN/METHODOLOGY: Ovid MEDLINE literature review (through March 2004) for all studies published in the English language and selected articles published in other languages such as French since 1963 using the medical subject heading terms "cough," "gastroesophageal reflux," and "gastroesophageal reflux disease." RESULTS: GERD, singly or in combination with other conditions, is one of the most common causes of chronic cough. In patients with normal chest radiographic findings, GERD most likely causes cough by stimulation of an esophageal-bronchial reflex. When GERD causes cough, there may be no GI symptoms up to 75% of the time. While 24-h esophageal pH monitoring is the most sensitive and specific test in linking GERD and cough in a cause-effect relationship, it has its limitations. In addition, there is no general agreement on how to best interpret the test, and it cannot detect non-acid reflux events. Therefore, when patients fit the clinical profile that has a high likelihood of predicting that GERD is the cause of cough, antireflux medical therapy should be empirically instituted. While some patients improve with minimal medical therapy, others require more intensive regimens. When empiric treatment fails, it cannot be assumed that GERD has been ruled out as a cause of chronic cough. Rather, an objective investigation for GERD is then recommended because the empiric therapy may not have been intensive enough or medical therapy may have failed. Surgery may be efficacious when intensive medical therapy has failed in selected patients who have undergone an extensive objective GERD evaluation. CONCLUSIONS: Accurately diagnosing and successfully treating chronic cough due to GERD can be a major challenge.

Chronic Disease↗
PubMed2006

Evaluation and outcome of young children with chronic cough.

OBJECTIVE: To evaluate the use of an adult-based algorithmic approach to chronic cough in a cohort of children with a history of > 3 weeks of cough and to describe the etiology of chronic cough in this cohort. METHODS: A prospective cohort study of children referred to a tertiary hospital with a history of > 3 weeks of cough between June 2002 and June 2004. All included children followed a pathway of investigation (including flexible bronchoscopy and evaluation of airway cytology via BAL) until diagnosis was made and/or their cough resolved. RESULTS: In our cohort of 108 young children (median age 2.6 years), the majority had wet cough (n = 96; 89%), and BAL fluid samples obtained during bronchoscopy led to a diagnosis in 45.4% (n = 49). The most common final diagnosis was protracted bacterial bronchitis (n = 43; 39.8%). These patients had neutrophil levels on BAL samples that were significantly higher than those in other diagnostic groups (p < 0.0001). Asthma, gastroesophageal reflux disease (GERD), and upper airway cough syndrome (UACS), which are common causes of chronic cough in adults, were found in < 10% of the cohort (n = 10). CONCLUSIONS: The adult-based anatomic pathway, which involves the investigation and treatment of patients with asthma, GERD, and UACS first is largely unsuitable for use in the management of chronic cough in young children as the common etiologies of chronic cough in children are different from those in adults.

Algorithms↗