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PubMed1981

Is cough as effective as chest physiotherapy in the removal of excessive tracheobronchial secretions?

The relative value of chest physiotherapy (including cough) and cough alone for the removal of excessive tracheobronchial secretions has been assessed in six patients with stable chronic obstructive lung disease. After labelling with inhaled radioactive tracer particles, clearance of secretions from selected central and peripheral lung regions was followed with a gamma camera linked to a computer. Cough alone and chest physiotherapy (including cough) were equally effective in the enhancement of central lung clearance. Physiotherapy but not cough along accelerated peripheral lung clearance (p less than 0.05). Sputum yield was greater during physiotherapy than during cough (p less than 0.05). These findings confirm the value of chest physiotherapy and high-light the limitation of cough in patients with excessive tracheobronchial secretion and impaired mucociliary clearance.

Bronchi↗
PubMed1990

Cough threshold after upper abdominal surgery.

The effect of upper abdominal surgery under general anaesthesia on the cough threshold was studied in 26 patients, on the basis of the concentrations of capsaicin and citric acid causing cough. Cough threshold was determined after administering doubling doses of nebulised aerosols of capsaicin and citric acid before operation and on the first and fourth postoperative days. There was an increase in cough threshold (decrease in cough sensitivity) in response to both inhaled irritants on the first postoperative day from the preoperative day and a return towards preoperative values by the fourth day after surgery. The increase in cough threshold on the first postoperative day correlated with the time since opiate administration (r = 0.7 for capsaicin, 0.52 for citric acid). These results show that the threshold concentration of chemical irritants causing cough is increased on the first postoperative day after upper abdominal surgery.

Abdomen↗
PubMed1994

Regional lung clearance during cough and forced expiration technique (FET): effects of flow and viscoelasticity.

BACKGROUND: In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance. This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique (FET) in patients with airways obstruction. METHODS: Nineteen patients (11 men and eight women) of mean (SE) age, % predicted FEV1, and daily sputum wet weight of 64 (2) years, 52 (6)%, and 37.5 (7.9) g respectively participated in the study. Mucus movement from proximal and peripheral lung regions was measured by an objective non-invasive radioaerosol technique. Each patient underwent three assessments: control, cough, and FET. During cough and FET, maximum expiratory flow was measured at the mouth level. Apparent viscosity and elasticity of the expectorated sputum samples were measured with a viscometer. RESULTS: Compared with the control run (mean (SE) clearance: 16 (3)%) there was an increase in clearance from the whole lung during cough (44 (5)%) and FET (42 (5)%), and also an enhanced clearance of inhaled, deposited radioaerosol from the trachea, inner and intermediate regions of the lungs, but not from the outer region. There were, however, no differences in regional clearance between cough and FET. Neither regional nor total clearance correlated with maximum expiratory flow, apparent viscosity, elasticity, or daily sputum wet weight. CONCLUSIONS: These results confirm that cough and FET both promote effective clearance but suggest that, unlike in vitro studies, sputum production and viscoelasticity, as well as maximum expiratory flow, provide no guide to clearance efficacy in humans.

Bronchiectasis↗
PubMed1998

Evaluation and outcome of patients with chronic non-productive cough using a comprehensive diagnostic protocol.

BACKGROUND: Asthma, post-nasal drip syndrome (PNDS), and gastro-oesophageal reflux (GOR) account for many cases of chronic non-productive cough (CNPC). Each may simultaneously contribute to cough even when clinically silent, and failure to recognise their contribution may lead to unsuccessful treatment. METHODS: Patients (all lifetime non-smokers with normal chest radiographs and spirometric measurements) referred with CNPC persisting for more than three weeks as their sole respiratory symptom underwent histamine challenge, home peak flow measurements, ear, nose and throat (ENT) examination, sinus CT scanning, and 24 hour oesophageal pH monitoring. Treatment was prescribed on the basis of diagnoses informed by investigation results. RESULTS: Forty three patients (29 women) of mean age 47.5 years (range 18-77) and mean cough duration 67 months (range 2-240) were evaluated. On the basis of a successful response to treatment, a cause for the cough was identified in 35 patients (82%) as follows: cough variant asthma (CVA) (10 cases), PNDS (9 cases), GOR (8 cases), and dual aetiologies (8 cases). Histamine challenge correctly predicted CVA in 15 of 17 (88%) positive tests. ENT examination and sinus CT scans each had low positive predictive values for PNDS (10 of 16 (63%) and 12 of 18 (67%) positive cases, respectively), suggesting that upper airways disease frequently co-exists but does not always contribute to cough. When negative, histamine challenge and 24 hour oesophageal pH monitoring effectively ruled out CVA and GOR, respectively, as a cause for cough. CONCLUSION: This comprehensive approach aids the accurate direction of treatment and, while CVA, PNDS and GOR remain the most important causes of CNPC to consider, a group with no identifiable aetiology remains.

Adolescent↗
PubMed1987

Effect of airway wall flexibility on clearance by simulated cough.

In our previous study, we investigated the relationship between mucus rheology, depth of mucus layer, and clearance by simulated cough. The purpose of the present study was to examine the effect of airway wall flexibility on the clearance of mucuslike gels. Transient airflows similar to cough were generated by both positive and negative pressure, the latter to mimic the dynamic compression that occurs during real cough. As in the previous study, the trachea was modeled as a trough of rectangular cross section with only the bottom lined with the mucus simulant. Clearance was followed by observing the displacement of marker particles. Since cough clearance is intimately related to wave formation in the mucus blanket, we hypothesized that clearance might be impeded if the wave formation occurred simultaneously in the wall and its lining layer. Thus, in one set of experiments the bottom rigid surface of the model trachea was replaced with a frame over which a flexible membrane could be drawn, whereas in the other set the rigid top was replaced by the frame. We also examined the effect of negative-pressure cough in excised canine tracheae, comparing the case where the tracheal membrane was free to deform vs. the case where it was secured. For the rigid-walled model, clearance by positive or negative pressure, with matched flow pattern, was the same. With the mucus simulant lining the flexible bottom surface, clearance increased with increasing membrane flexibility for negative-pressure cough and decreased for positive-pressure cough.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Afferent neural pathways in cough and reflex bronchoconstriction.

Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents. These two reflexes can be evoked both from the larynx and tracheobronchial tree and also from some extrarespiratory sites. Within the airways, certain sites are particularly sensitive to stimulation of cough (larynx and points of proximal airway branching), whereas bronchoconstriction can be triggered from the whole of the tracheobronchial tree. In the larynx, "irritant" receptors with myelinated afferents mediate cough and bronchoconstriction. Little seems to be known about laryngeal nonmyelinated afferents and their reflexes. In the tracheobronchial tree and lung, slowly adapting stretch receptors (SARs) and rapidly adapting stretch receptors (RARs) have opposing effects on airway tone, the former mediating bronchodilation and the latter bronchoconstriction. In cough, on the other hand, they operate concurrently, a mediatory role for RARs and a facilitatory role for SARs. C-fiber endings (bronchial and pulmonary) mediate bronchoconstriction. Inhalation of so-called "selective" C-fiber stimulants induces cough, but excitation of RARs has not been eliminated, and the possibility also exists that the cough is secondary to other lung actions mediated by these nerve endings. Although cough and bronchoconstriction may be mediated by the same type of receptor, they seem to have separate afferent neural pathways.

Afferent Pathways↗
PubMed1991

Fictive cough in the cat.

Experiments were performed to determine whether cough could be elicited in paralyzed cats ventilated on a respiratory cycle-triggered pump. Midcollicular decerebrate cats were paralyzed and artificially ventilated on a phrenic-triggered pump. Phrenic and cranial iliohypogastric nerve efferent activities were recorded. Cough was elicited by electrical stimulation of the superior laryngeal nerve (SLN) or probing the intrathoracic trachea. Fictive coughs induced by electrical stimulation of the SLN or mechanical stimulation of the intrathoracic trachea consisted of large-amplitude bursts in phrenic discharge immediately followed by large bursts in cranial iliohypogastric discharge. During fictive cough, phrenic postinspiratory discharge was reduced relative to control cycles. Codeine (0.03-1 mg/kg iv) decreased both SLN- and probe-induced fictive cough. I conclude that fictive cough can be produced in paralyzed cats ventilated on a phrenic-triggered pump. Furthermore, fictive cough can be produced in the absence of afferent feedback associated with active expiration.

Afferent Pathways↗
PubMed1993

Effects of 5-hydroxytryptamine and 5-hydroxytryptophan infusion on the human cough reflex.

In some species serotonin (5-HT) has been shown to act as a central modulator of the cough reflex. To investigate whether serotonergic mechanisms influence the control of the human cough reflex, we have induced cough responses before and during infusions of 5-HT; its precursor 5-hydroxytryptophan (5-HTP), which, in contrast to 5-HT, crosses the blood-brain barrier; and saline control. At the start of each study day, eight normal male volunteers were challenged with a single inhalation of a solution lacking chloride ions (0.15 M sodium bicarbonate) and a single breath of capsaicin during a sham infusion. After 3 h they received repeat cough challenges during experimental infusions of 5-HT, 5-HTP, or saline control, which were given randomly and single blind. Heart rate, respiratory rate, and blood pressure were measured before, during, and after each infusion. Both 5-HT and 5-HTP reduced cough responses to the chloride-deficient solution (P = 0.035 and P = 0.017, respectively) with respect to saline control, whereas neither infusion reduced responses to capsaicin. 5-HT caused a transient increase in heart rate that was not observed with a similar dose of 5-HTP or saline (P < 0.01). Respiratory rate and blood pressure were not affected by experimental infusions but rose during cough challenge. We conclude that 5-HT exerts an inhibitory influence over the human cough reflex at peripheral and possibly central sites.

5-Hydroxytryptophan↗
PubMed1998

Seasonal chronic cough with sputum eosinophilia caused by Trichosporon cutaneum (Trichosporon asahii).

The case of a 46-year-old man with a chronic cough with sputum eosinophilia (atopic cough) caused by Trichosporon cutaneum serotype II (Trichosporon asahii) is reported. The diagnosis was made with the inhalation challenge test with T. asahii antigen. He was admitted for the diagnosis and treatment of a severe nonproductive cough in the summer season. Although his sputum contained 13% eosinophils of nucleated cells, he did not have bronchial hyperresponsiveness to methacholine or a heightened bronchomotor tone. Bronchodilator therapy was not effective for his cough. His symptoms worsened on returning home, suggesting the existence of some etiologic agent in his house. A high titer of serum anti-Trichosporon antibody was detected and antigen provocation test with the Trichosporon extract was positive: the development of a cough 6 h later and a decrease in the cough threshold to inhaled capsaicin 48 h later (7.85 microM from 31.3 microM prechallenge). This is the first report on a chronic cough with sputum eosinophilia induced by T. cutaneum (T. asahii).

Chronic Disease↗
PubMed2001

Effects of candesartan on cough and bronchial hyperresponsiveness in mildly to moderately hypertensive patients with symptomatic asthma.

BACKGROUND: Candesartan, an AT(1) receptor antagonist, has been reported to have no association with persistent cough in subjects with hypertension, but there has been no study on the safety of its administration to hypertensive patients with symptomatic asthma. The aim of this study was to compare the adverse effects of candesartan and calcium antagonists on cough, pulmonary function, and bronchial hyperresponsiveness in these patients. METHODS AND RESULTS: Sixty mildly to moderately hypertensive patients with bronchial asthma received either candesartan (n=30) or the calcium antagonists nifedipine or manidipine (n=30) for 6 months. The candesartan group included 5 subjects with a history of ACE inhibitor-induced cough. There were no differences between the 2 groups in patient characteristics, ACE gene polymorphism, pulmonary function, or bronchial hyperresponsiveness to methacholine. Control of hypertension was the primary end point; new cough detected by self-administrated questionnaire and an increase in cough frequency by visual analog scale were the second end point. No patient complained of persistent cough. Neither mean visual analog scale score nor pulmonary functions changed during this study. Bronchial hyperresponsiveness had a tendency to improve in the candesartan group, but there was no difference between the 2 groups. CONCLUSIONS: Incidence, frequency, and severity of persistent cough, pulmonary functions, and bronchial hyperresponsiveness did not change in either the candesartan or calcium antagonist group. It is suggested that candesartan is as effective and safe as calcium antagonists in the treatment of hypertension associated with symptomatic asthma.

Adult↗
PubMed1994

Airway inflammation in nonasthmatic subjects with chronic cough.

The physiopathology of chronic cough remains obscure. We evaluated the possibility that chronic cough in nonasthmatic subjects is associated with airway inflammation, and if this is so, what the relationship between this inflammation and the possible etiology of cough might be, as well as its response to inhaled steroids. Nineteen nonsmoking, nonasthmatic subjects referred for a persistent cough (mean: 3.8 yr) were evaluated and compared with 10 normal subjects. The evaluation included a respiratory questionnaire, a physical examination, allergy skin-prick tests, chest and sinus radiographs, esophageal pH monitoring, measurements of expiratory flows, methacholine and citric acid challenges, and flexible bronchoscopy for bronchoalveolar lavage (BAL) and bronchial biopsies. Fourteen subjects further accepted participation in a randomized, double-blind crossover trial of inhaled beclomethasone (500 micrograms four times daily) and a placebo for 1 mo each. Four groups of subjects were identified according to the presence of postnasal discharge (n = 4), gastroesophageal reflux (n = 6), both conditions (n = 5), or neither (n = 4). Subjects with chronic cough had an increased number of inflammatory cells in their bronchoalveolar lavage fluid (BALF), but there was no significant difference between the four subgroups of coughers. As compared with control subjects, the bronchial biopsies of subjects with chronic cough showed increased epithelial desquamation (p = 0.004) and inflammatory cells (p = 0.005), particularly mononuclear cells (p < 0.01), in addition to submucosal fibrosis, squamous-cell metaplasia, and loss of cilia. These findings were not significantly different between the different etiologic groups. In subjects with chronic cough, basement-membrane thickness was normal and not different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Exhaled nitric oxide as a noninvasive assessment of chronic cough.

Exhaled nitric oxide (ENO) has been suggested as a marker of airway inflammation. This study aimed to evaluate the role of ENO in the investigation of chronic cough. We measured ENO in 38 adult patients reporting chronic cough, in 23 healthy control subjects, and in 44 asthmatics. In addition to the regular investigation, ENO was measured by a chemiluminescent analyzer using the restricted breath technique. In the chronic cough group, 30 were considered as nonasthmatic, whereas asthma was diagnosed in eight by a positive methacholine challenge. ENO values were significantly higher in patients with chronic cough attributable to asthma as compared with those with chronic cough not attributable to asthma and to healthy volunteers (75.0 ppb; 16.7 ppb; and 28.3 ppb, respectively). The sensitivity and specificity of ENO for detecting asthma, using 30 ppb as the ENO cutoff point, were 75 and 87%, respectively. The positive and negative predictive values were 60 and 93%, and the positive and negative likelihood ratios were 5.8 and 0.3, respectively. We conclude that ENO may have a role in the evaluation of chronic cough. In this group of patients, low ENO suggested little likelihood of asthma. The patients with chronic cough not attributable to asthma showed a low ENO value as compared with healthy volunteers and asthmatics.

Adult↗
PubMed1999

Effect of aerosolized uridine-5'-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance. Because patients with PCD use cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5'-triphosphate (UTP) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells. We measured clearance during cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml). Clearance during cough (whole lung) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min. Safety parameters were recorded during and after drug delivery. Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle (from 0 to 60 min: 0.40 +/- 0.07%/min [UTP] versus 0.26 +/- 0. 04%/min [vehicle] [mean +/- SEM], p = 0.01), and from 0 to 120 min: 0.38 +/- 0.05%/min [UTP] versus 0.25 +/- 0.04%/ min [vehicle], p = 0. 02). Aerosolized UTP is safe, with no serious adverse effects. Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP.

Administration, Inhalation↗
PubMed2001

Airway eosinophilia is associated with wheeze but is uncommon in children with persistent cough and frequent chest colds.

The role of eosinophilic airway inflammation in the variant asthma syndromes of cough and chest colds is not well defined. We tested the hypothesis that children with persistent cough and chest colds have increased sputum eosinophils, similar to those with wheeze. The parents of 390 primary school children completed a symptoms questionnaire. Children with wheeze (n = 28), cough (n = 12), recurrent chest colds (n = 17), and no symptoms (control subjects, n = 26), underwent allergy skin prick tests, spirometry, hypertonic saline inhalation challenge, and sputum induction, and then completed a peak expiratory flow (PEF) and symptoms diary over a 2-mo period. Children with wheeze had significantly reduced PEF (p = 0.001) and higher sputum eosinophils when compared with the cough, chest cold, and control groups (3.1% versus 0.5%, 0%, 0%; p = 0.03). The prevalence of eosinophilic bronchitis (sputum eosinophils > 2.5%) was 45% in the wheeze group, which was significantly higher than the control group (9.35%, p = 0.04). Eosinophilic bronchitis was present in two children with cough (20%) and two with chest colds (15%, p > 0.05 versus control). In these groups, eosinophilic bronchitis was not associated with airway hyperresponsiveness (AHR) to hypertonic saline (p > 0.05). Children with cough and chest colds reported greater exposure to environmental tobacco smoke. In conclusion, this community-based survey of children with chronic respiratory symptoms has shown that wheeze is a good discriminator for the presence of eosinophilic bronchitis, and that persistent cough and recurrent chest colds without wheeze should not be considered a variant of asthma. Eosinophilic bronchitis did occur in a significant minority of these "variant asthma" syndromes.

Age Factors↗
PubMed2003

Cough gastric pressure and maximum expiratory mouth pressure in humans.

Maximal expiratory mouth pressure is a well established test that is used to assess expiratory muscle strength. However, low values are difficult to interpret, as they may result from technical difficulties in performing the test, particularly in patients with facial muscle weakness or bulbar dysfunction. We hypothesized that measuring the gastric pressure during a cough, a natural maneuver recruiting the expiratory muscles, might prove to be a useful additional test in the assessment of expiratory muscle function. Mouth expiratory and cough gastric pressures were measured in 99 healthy volunteers to obtain normal values and in 293 patients referred for respiratory muscle assessment to compare the two measurements. Between-occasion within-subject coefficient of variation, assessed in 24 healthy volunteers, was 10.3% for mouth pressure and 6.9% for cough. Mean +/- SD cough gastric pressure for normal males was 214.4 +/- 42.2 and 165.1 +/- 34.8 cm H2O for females. In 171 patients deemed weak by a low mouth expiratory pressure, 42% had a normal cough gastric pressure. In 105 patients deemed weak by a low cough gastric pressure, 5.7% had a normal expiratory mouth pressure. Low maximal expiratory mouth pressures do not always indicate expiratory muscle weakness. Cough gastric pressure provides a useful complementary test for the assessment of expiratory muscle strength.

Case-Control Studies↗
PubMed2002

Relationship between supramaximal flow during cough and mortality in motor neurone disease.

The main function of cough is clearance of intrathoracic airways. A normal cough is characterized by a transient increase in expiratory flow above the maximal flow-volume loop envelope, known as cough "spikes". They may be absent in patients with motor neurone disease. The relationship between cough pattern, pulmonary function and survival was studied. Fifty-three patients were recruited (25 bulbar). Vital capacity, maximal inspiratory and expiratory mouth pressures and cough flow/volume curves were performed on all patients, and the presence or absence of spikes were recorded. The primary endpoints were mortality or initiation of ventilatory support over a period of 18 months. Thirty-five patients died over the 18-month period of the study (including the six who were started on noninvasive ventilation). Twelve of the 24 patients with spikes died compared to 23 out of 29 patients without spikes (p<0.05). Patients without spikes were more likely to be bulbar on clinical grounds (p<0.0001) and had poorer lung function. The results showed an association between the absence of cough spikes and increased mortality. However the main determinants of survival in motor neurone disease are age, vital capacity and inspiratory mouth pressure, and it remains to be shown whether regular monitoring of cough conveys any additional advantage.

Adult↗
PubMed1995

Neurophysiology of the cough reflex.

Cough is due to activation of sensory receptors in the larynx and lower respiratory tract, sending impulses to the brainstem. The central organization of cough is poorly understood. The afferent pathways for cough are from receptors in and under the epithelium of the airways. These receptors are rapidly adapting, with thin myelinated fibres in the vagus nerves, which can be directly stimulated by tussive agents. Activation of C-fibre receptors in the airway releases sensory neuropeptides. These cause neurogenic inflammation and may activate rapidly adapting receptors to cause cough. The central connections of the C-fibre receptors inhibit cough. Thus, the sensitivity of the cough reflex and its pattern of response is due to a complex interaction between C-fibre receptors and rapidly adapting receptors, with peripheral and central nervous interactions. How these mechanisms apply to clinical cough in patients is at present poorly understood, but is beginning to be clarified.

Afferent Pathways↗