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Biomedical subjects

P V Dicpinigaitis

Publications and source records attributed to P V Dicpinigaitis.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2004

Cough. 4: Cough in asthma and eosinophilic bronchitis.

Airway eosinophilia and cough may be associated with asthma and with non-asthmatic eosinophilic bronchitis. Whether cough variant asthma and eosinophilic bronchitis are distinct entities or a pathophysiological spectrum needs further examination.

Asthma↗
PubMed2001

Effect of the cyclooxygenase-2 inhibitor celecoxib on bronchial responsiveness and cough reflex sensitivity in asthmatics.

Cyclooxygenase (COX), an essential enzyme in the pathway of prostaglandin formation from arachidonic acid, exists in two isoforms. Cyclooxygenase-1 (COX-1) is expressed under normal physiologic conditions, whereas COX-2, the inducible isoform, is associated with inflammation. Recent studies have linked COX-2 induction to the asthmatic inflammatory response, but potentially beneficial results, such as enhanced production of antiinflammatory and bronchoprotective substances, may also occur. The aim of the present study was to investigate the effect of selective COX-2 inhibition on bronchial responsiveness and cough reflex sensitivity. Eight adult subjects with stable asthma underwent spirometry, bronchoprovocation challenge with methacholine, and cough challenge testing with capsaicin, before and after a 7 day course of the COX-2 inhibitor celecoxib (200 mg orally, twice daily) and placebo, in a randomized, double-blind, crossover fashion. No significant changes in pulmonary function, bronchial responsiveness, or cough reflex sensitivity were induced by celecoxib. It appears, therefore, that 1 week of therapy with celecoxib does not significantly affect basal airway tone, nor the afferent airway receptors controlling bronchoconstriction and cough. However, the results of this trial cannot be extrapolated to subjects with severe asthma, or those suffering an asthmatic exacerbation. In such conditions of enhanced inflammatory response, the role of selective COX-2 inhibition remains to be elucidated.

Adult↗
PubMed2001

Ethnic and gender differences in cough reflex sensitivity.

BACKGROUND: Although recent studies have suggested that the cough reflex is more sensitive in women than in men, ethnic differences in cough reflex sensitivity have not previously been investigated. OBJECTIVES: To evaluate ethnic and gender differences in cough reflex sensitivity. METHODS: We performed capsaicin cough challenge testing in 182 healthy volunteers of three distinct ethnic groups: Caucasian (white, non-Hispanic, of European origin), Indian (originating from the Indian subcontinent) and Chinese. The concentration of capsaicin inducing 2 or more (C2) and 5 or more coughs (C5) was determined in each subject. RESULTS: Mean (+/-SEM) values for log C5 demonstrated that, within each ethnic group, the cough reflex was more sensitive in women: p = 0.00002 for Caucasian subjects; p = 0.003 for Indian volunteers; and p = 0.002 for Chinese subjects. Examination of C2 data yielded similar results. When subjects were evaluated by gender, multivariate analysis of variance demonstrated no ethnic differences in sensitivity to capsaicin. CONCLUSION: Our data do not support the presence of significant ethnic differences in cough reflex sensitivity, but do confirm previous data demonstrating lower cough thresholds in women.

Administration, Inhalation↗
PubMed2000

Baclofen-induced cough suppression in cervical spinal cord injury.

OBJECTIVE: To determine the effect of the GABA-agonist baclofen on cough reflex sensitivity in subjects with cervical spinal cord injury (C-SCI). Baclofen has been shown to inhibit the cough reflex in able-bodied volunteers. DESIGN: Prospective, nonrandomized control trial. SETTING: Veterans Affairs medical center with large outpatient SCI population. PARTICIPANTS: Twelve adult males (11 outpatients) with C-SCI chronically maintained on oral baclofen for the treatment of muscle spasm. INTERVENTION: Subjects underwent cough challenge testing with inhaled capsaicin. The concentrations (microM) of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs were determined. Mean values for log C2 and log C5 were compared with a control group of outpatients with C-SCI not receiving baclofen. RESULTS: Subjects treated with baclofen had a significantly higher cough threshold (diminished cough reflex sensitivity) than control subjects. Mean (+/- standard error of the mean) values for log C2 in study subjects and controls were 1.28 +/- .16 and .65 +/- .15, respectively (p = .009). Mean values for log C5 in subjects receiving baclofen and in control subjects were 2.20 +/- .22 and 1.43 +/- .23, respectively (p = .024). Subjects and controls did not differ in terms of age, spirometric parameters, or duration of injury. CONCLUSIONS: The results suggest that chronic therapy with baclofen diminishes cough reflex sensitivity in subjects with C-SCI. The clinical significance of this finding remains to be elucidated.

Adult↗
PubMed1999

Effect of the GABA-agonist baclofen on bronchial responsiveness in asthmatics.

Gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitter. Recently, the presence of GABA and its receptors has been confirmed in peripheral tissues, including the lungs. GABA and the GABA agonist baclofen have been shown in animal studies to inhibit airway responsiveness to various bronchoconstricting agents. The results of these investigations suggest the possibility of a role for baclofen in the therapy of human airway hyperreactivity. To investigate this question, a randomized, double-blind, placebo-controlled, cross-over study was performed to evaluate the effect of a 14-day course of oral baclofen (10 mg three times daily) on pulmonary function and bronchial responsiveness to methacholine in a group of six stable asthmatics. In five of six subjects, hyperresponsiveness was enhanced after therapy with baclofen. Mean (+/- SEM) log PC(20)pre-and post-baclofen were 0.160 +/- 0.247 and -0.223 +/- 0.282, respectively (P=0.023). Baseline pulmonary function (FEV(1)) was unaffected by baclofen. The mechanism(s) underlying this apparent paradoxical enhancement by baclofen of bronchial responsiveness remains speculative, but may be relevant to the recently-proposed concept of dysfunction in asthmatics of prejunctional GABA receptors, whose normal role may be to inhibit cholinergic contraction of bronchial smooth muscle.

Adult↗
PubMed1999

"Crack" cocaine-induced syndrome mimicking sarcoidosis.

A 39-year-old man with a history of frequent "crack" cocaine use of several years' duration presented with progressive dyspnea. Evaluation revealed bilateral interstitial pulmonary infiltrates and hilar adenopathy, diffuse pulmonary uptake of gallium, and markedly elevated serum angiotensin-converting enzyme activity. Open lung biopsy revealed interstitial and perivascular collections of histiocytes containing refractile, polarizable material, presumably inhaled along with the cocaine. Paratracheal lymph nodes were enlarged, reactive, and contained similar polarizable material. The well-formed, non-necrotizing granulomata characteristic of sarcoidosis were not present in either tissue specimen. To our knowledge, the association of chronic crack cocaine inhalation with this constellation of clinical findings, typically seen in sarcoidosis, has not previously been described.

Adult↗
PubMed1999

Cough reflex sensitivity in subjects with cervical spinal cord injury.

An effective cough requires an intact cough reflex as well as adequate respiratory muscle function to generate elevated intrathoracic pressures. Since the major muscles of expiration are innervated by the first thoracic segment and below, transection of the cervical spinal cord results in severely compromised expiratory function and cough. To investigate the effects of cervical spinal cord injury (C-SCI) on cough reflex sensitivity, we measured responsiveness to inhaled capsaicin in 12 male subjects with chronic C-SCI and compared findings to those from a control group of 50 able-bodied men. The concentrations (microM) of capsaicin inducing two or more (C2) and five or more coughs (C5) did not significantly differ between the two groups. Mean (+/- SEM) values for log C2 in subjects with C-SCI and control subjects were 0.65 +/- 0.15 and 0.87 +/- 0.07, respectively (p = 0.15). Mean values for log C5 in subjects with C-SCI and control subjects were 1.43 +/- 0.23 and 1.41 +/- 0.08, respectively (p = 0.94). We conclude that cough reflex sensitivity is preserved after C-SCI, and that ineffective cough in this population results primarily from the loss of innervation of respiratory muscles.

Adult↗
PubMed1999

Effect of zafirlukast on cough reflex sensitivity in asthmatics.

In patients with asthma, increased sensitivity of airway sensory nerves may be involved in producing bronchospasm and cough. To evaluate the effect of a leukotriene-modifying agent on cough reflex sensitivity, we measured the cough response to inhaled capsaicin before and after a 1 4-day course of therapy with zafirlukast, a cysteinyl leukotriene receptor antagonist, in a group of stable asthmatics. The concentration of capsaicin inducing two or more (C2) and five or more (C5) coughs was not altered by zafirlukast, even in those subjects demonstrating a significant change (increment or decrement) in forced expiratory volume in 1 sec (FEV1). These findings support previous evidence that cough and bronchoconstriction are modulated by distinct neural pathways.

Administration, Oral↗
PubMed1998

Inhibition of capsaicin-induced cough by the gamma-aminobutyric acid agonist baclofen.

Gamma-aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also exists in the lungs. The GABA-agonist baclofen has been shown to have antitussive activity via a central mechanism in animals. Recently it was demonstrated that a 14-day course of baclofen given three times daily significantly inhibits the cough reflex in healthy volunteers. Because of the prolonged antitussive effect of baclofen that has been previously observed, the present study was conducted to evaluate the antitussive effect of low-dose, oral baclofen given once daily. Forty-one healthy volunteers were randomly assigned in a double-blind manner to receive a 28-day course of baclofen, either 10 mg or 20 mg once daily, or placebo. Subjects underwent cough challenge testing with inhaled capsaicin to establish baseline cough reflex sensitivity, and subsequently after 14 and 28 days of therapy. Subjects receiving baclofen 20 mg daily demonstrated significant inhibition of cough sensitivity after 14 days and after 28 days of therapy compared with baseline. Neither placebo nor baclofen 10 mg daily had a significant effect on cough sensitivity. No serious side effects were experienced by any study participant. These results confirm the recent observation that baclofen has significant antitussive activity in humans. Further, once-daily administration of a relatively low dose of baclofen is sufficient to achieve significant cough inhibition, although at least 14 to 28 days of therapy may be required to attain maximal antitussive effect. These results support further investigation of baclofen or other GABA-agonists as potential therapeutic agents for chronic, nonproductive cough.

Administration, Oral↗
PubMed1998

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↗
PubMed1998

The influence of gender on cough reflex sensitivity.

BACKGROUND: The more common occurrence in women of cough due to angiotensin-converting enzyme inhibitors raises the possibility of gender-related differences in the sensitivity of the cough reflex. Of two recent studies that evaluated cough response to inhaled capsaicin in normal subjects, one demonstrated heightened sensitivity of the cough reflex in women compared with men, while the other revealed no gender-related differences. To further investigate this question, we reviewed our experience with cough challenge testing in normal volunteers. STUDY OBJECTIVE: To compare cough reflex sensitivity in healthy adult female and male subjects. DESIGN: Retrospective data analysis. SETTING: Academic medical center. PARTICIPANTS: One hundred healthy volunteers (50 male, 50 female). INTERVENTIONS: Subjects inhaled capsaicin in ascending, doubling concentrations until the concentration inducing five or more coughs (C5) was reached. In addition, the concentration inducing two or more coughs (C2; cough threshold) was measured. RESULTS: Mean log C5 was significantly lower in women than in men: 1.02+/-0.09 (SEM) microM vs 1.41+/-0.08 microM, respectively (p=0.002). Log C2 (cough threshold) was also significantly lower in female subjects: 0.534+/-0.068 microM vs 0.870+/-0.065 microM in male subjects (p=0.00058). CONCLUSION: Healthy women have a more sensitive cough reflex than do healthy men. The reasons for this significant gender difference remain to be elucidated, but may involve a heightened sensitivity, in women, of the sensory receptors within the respiratory tract that mediate cough.

Administration, Inhalation↗
PubMed1997

Antitussive effect of the GABA-agonist baclofen.

BACKGROUND: gamma-Aminobutyric acid (GABA) is a central inhibitory neurotransmitter that also exists in peripheral tissues, including the lung. The GABA-agonist baclofen has been shown, in animal studies, to inhibit cough via a central mechanism, but has not been investigated in humans (to our knowledge). STUDY OBJECTIVE: To evaluate the antitussive effect of baclofen in normal human subjects. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Academic medical center. PARTICIPANTS: Twenty healthy, adult volunteers. INTERVENTIONS: Subjects underwent cough challenge with inhaled capsaicin before and after a 14-day course of baclofen, 10 mg three times daily, or placebo. Capsaicin cough threshold (C5) was defined as the concentration of inhaled capsaicin inducing five or more coughs. RESULTS: Subjects receiving baclofen (n=10) demonstrated a significant elevation of capsaicin cough threshold compared with placebo subjects (n=10). Mean delta log C5 after treatment was 0.48+/-0.19 (SEM) for the baclofen group, and -0.06+/-0.12 for the placebo group (p=0.024). Six of 10 subjects receiving baclofen, but none of the 10 subjects receiving placebo, demonstrated a fourfold or greater increase in capsaicin cough threshold (p=0.0054). CONCLUSION: The antitussive activity of low-dose, oral baclofen demonstrated in this study supports further investigation of this drug, or other GABA-agonists, for a potential therapeutic role in the treatment of pathologic cough.

Adult↗
PubMed1996

Effect of angiotensin-converting enzyme inhibition on bronchial responsiveness.

The effect of angiotensin-converting enzyme (ACE) inhibition on bronchial responsiveness has not been clearly established. Because ACE degrades bradykinin and substance P, inhibition of the enzyme may lead to accumulation of these potent bronchoconstrictors in the lung, potentially leading to enhanced bronchial reactivity or bronchospasm. Previous studies of the effect of ACE inhibition on airway responsiveness have yielded conflicting results. A randomized, double-blind, placebo-controlled study was therefore conducted to evaluate the effect of a 14-day course of oral lisinopril (10 mg for days 1-3, 20 mg for days 4-14) on bronchial responsiveness to inhaled methacholine in a group of healthy volunteers. No significant change in methacholine responsiveness occurred in any of the participants receiving lisinopril. The mean ( +/- SD) concentration of methacholine producing a decrease in FEV1 of 20% from baseline (PC20; mg/mL) was 23.3 +/- 5.0 before the study and 23.5 +/- 4.5 at the end of the study for the lisinopril group, and 23.0 +/- 4.6 before the study and 21.8 +/- 6.9 after the study for the placebo group. The 14-day course of ACE inhibitor therapy did not enhance nonspecific bronchial responsiveness in healthy volunteers.

Administration, Inhalation↗
PubMed1996

Use of baclofen to suppress cough induced by angiotensin-converting enzyme inhibitors.

OBJECTIVE: To determine whether baclofen can suppress the cough induced by angiotensin-converting enzyme (ACE) inhibitors. DESIGN: Prospective, open-label, clinical trial of a 4-week course of low-dose oral baclofen (5 mg tid days 1-7, 10 mg tid days 8-28). SUBJECTS: Seven patients with severe, persistent ACE inhibitor-induced cough. SETTING: University-affiliated teaching hospital. MAIN OUTCOME MEASURES: Study participants kept daily diaries monitoring the frequency of cough during and after completion of baclofen therapy. RESULTS: All subjects demonstrated diminution of cough after initiation of baclofen. Initial improvement was noted by a mean of 4.0 days (range 3-6), and maximal improvement during treatment was achieved by a mean of 10.7 days (range 5-15). In addition, all subjects demonstrated persistent suppression of cough (range 25-74 d) after discontinuation of the study drug. CONCLUSIONS: Low-dose oral baclofen therapy caused a prolonged antitussive effect in all subjects without inducing any adverse reactions. Baclofen may offer an alternative to the discontinuation of ACE inhibitor therapy in patients for whom these drugs are required.

Adult↗