Induction Of Cough Research Articles

A Retrospective Study Analyzing the Incidence of Urine Incontinence after Cesarean Section Delivery in Comparison with Vaginal Delivery

Introduction: Urine incontinence is the involuntary leakage of urine. Its actual prevalence is underestimated. There is a general belief that vaginal delivery is a major risk. Elective cesarean delivery is increasing worldwide; one reason is to protect against pelvic floor disorders, including urine incontinence. Previous studies included small samples with controversial results. This study aimed to compare the risk of urine incontinence in women who had cesarean delivery with those who had vaginal delivery. Methods: It was a retrospective study on 1751 women delivered in a university hospital over a 5- year period. Data collected on number of deliveries, age at first and last delivery, mode of each delivery, gestational age, birth weight, indication of cesarean section, induction of labor, episiotomy, perineal tears, smoking, chronic cough, chronic constipation, presence and severity of urine incontinence using ICIQ score. Patients were categorized into 2 groups: all cesarean section deliveries and at least one vaginal delivery. Results: A total of 600 respondents delivered only by cesarean section, and 1151 had at least one vaginal delivery. Urine incontinence prevalence in the cesarean group was 5.8%, and 6.9% in the vaginal group. Age, perineal tear, chronic cough, and chronic constipation were found to be significantly associated with urinary incontinence. After adjusting for all other variables, vaginal delivery was not found to be significantly associated with incontinence compared to cesarean. Conclusion: Vaginal and cesarean deliveries have a comparable incidence of urinary incontinence. It is difficult to get a firm conclusion on whether cesarean is protective. Chronic constipation and cough are important factors regardless of delivery mode.

Antitussive properties of aqueous extracts of Sterculia setigera Delile (Sterculiaceae) and mixture of Aframomum melegueta K. Schum (Zingiberaceae) - Citrus aurantifolia (Christm. and panzer) Swingle (Rutaceae)

Sterculia setigera, Aframomum melegueta and Citrus aurantifolia are plants commonly used in African traditional medicine and especially in Benin to treat cough and asthma. The Phytochemical analysis of aqueous extracts of these plants, based on methods of precipitation and differential staining, revealed the presence of alkaloids, tannins, flavonoids, anthocyanins, leuco-anthocyanins, mucilages and reducing compounds. The presence of essential oils is found only in the mixture. The orally administration of aqueous extracts before induction of cough by inhalation of vapor 10 mL of 20% citric acid in Cavia porcellus (Guinea Pigs) inhibits the cough significantly with dose compared to the control and reference : Neo-codion ®. The extract of mixture Aframomum melegueta - Citrus aurantifolia (AMCA) was more active than Sterculia setigera’s (SS). These results confirm that aqueous extracts of Sterculia setigera and mixture Aframomum melegueta - Citrus aurantifolia, used in traditional medicine in Benin, have antitussive properties.

Induction of airway remodeling and persistent cough by repeated citric acid exposure in a guinea pig cough model

BackgroundA previous study involving guinea pigs showed that repeated cough could increase peripheral airway smooth muscle area, which can also aggravate cough. The airway pathologic changes produced by prolonged cough are still unknown. ObjectiveTo study the airway pathologic changes in prolonged cough models of guinea pigs. MethodsGuinea pigs were assigned to three treatment groups: citric acid inhalation (CA) alone, citric acid inhalation with codeine pretreatment (COD), or saline solution inhalation (SA). Animals were challenged with citric acid or saline solution three times weekly. The intervention period was 22 or 43 days. Animals were challenged with citric acid on the first and last days of exposure. Lung specimens were obtained for pathologic analysis 72 h after the last exposure. ResultsCompared with the other two groups, the CA group had increased frequency of cough on both 22 and 43 days of exposure. Tracheal basement membrane (BM) thickness was increased after 43 days of exposure, correlating with the frequency of cough. The area of airway smooth muscles (ASM index) in small airways increased in the CA group after both 22 and 43 days of exposure, compared with the SA group. Compared with the COD group, the ASM index in small airways increased in the CA group after 22 days of exposure instead of 43 days of exposure. ConclusionsAn increase in peripheral smooth muscle area by repeated cough was confirmed. Moreover, this is the first study to show that tracheal BM thickness increased after prolonged exposure (43 days). Repeated cough may lead to airway remodeling, which was also associated with an increased frequency of cough.

The effect of pH on citric acid cough challenge: A randomised control trial in chronic cough and healthy volunteers

IntroductionCitric acid has been used for over six decades to induce cough; however the mechanism of its pro-tussive effect is still not fully understood. We assessed the response to inhalation of citric acid at varying levels of acidity to determine if the pH of the solution plays a role in the induction of cough. Data was collected from both healthy volunteers and patients with chronic cough. Methods20 chronic cough patients and 20 healthy volunteers were recruited and underwent three cough challenges on separate days. Each visit involved 5 repeated one second inhalations of 300 mM citric acid solution. The concentration of the citrate cation remained constant, but the pH of the solution altered by the addition of sodium bicarbonate to 3, 5 and 6, representing the pKa values of the individual acid moieties. The total number of coughs elicited was recorded for each inhalation. ResultsTwo subjects withdrew and were not included in the analysis. Participants were gender matched, each group consisting of 12 females. 74% of chronic coughers coughed at pH 3 (mean coughs 16), 89% coughed at pH 5 (18) and 63% coughed at pH 6 (7). In healthy volunteers, 60% of subjects coughed at pH 3 (9), 30% of subjects coughed at pH 5 (3), and 10% of subjects coughed at pH 6 (0). Thus chronic cough patients coughed more than healthy volunteers and did not exhibit a clear pH concentration response. There was also a greater variability in their response to individual challenges.

The research of the possible mechanism and the treatment for capsaicin-induced cough

Unexplained chronic cough (UCC) affects millions of patients worldwide. New therapeutic approaches to this condition are urgently needed, since current treatment options provide only symptomatic relief. Cough reflex hypersensitivity has been shown to play an important role in the pathogenesis of UCC. The transient receptor potential vanilloid type 1 (TRPV1) is present on peripheral terminals of airway sensory nerves and modulation of its activity represents a potential target for the pharmacological treatment of UCC. The aim of this study was to explore the efficacy and the possible mechanism of SB705498, a TRPV1 antagonist, for cough in a capsaicin-induced cough animal model (i.e. guinea pigs). Induction of cough by capsaicin was successfully implemented in the guinea pigs, and the animals that met the inclusion criteria were randomly divided into four treatment groups: (1) Saline inhalation group (NSInh group, N = 10, negative control group), (2) Codeine phosphate intraperitoneal injection group (CPInp group, N = 10, positive control group), (3) SB705498 inhalation group (SBInh group, N = 10), (4) SB705498 intragastric administration group (SBIng group, N = 10). After treatment with above compounds, the capsaicin-induced cough experiment was performed again. The cough numbers and the cough incubation periods were recorded to evaluate the antitussive effect of SB705498. Enzyme-linked immunosorbent assay (ELISA) testing and Immunohistochemistry (IHC) staining for substance P (SP), calcitonin gene related peptide (CGRP) and neurokinin A (NKA) expression in lung and brain tissues were performed as an indication of neurogenic inflammation. Hematoxylin-Eosin (H&E) staining was used to observe the pathology morphology of lung and brain tissues. When the CPInp, SBInh and SBIng groups were compared to the NSInh group, the cough numbers were significantly reduced (p < .001), while the cough incubation periods were significantly prolonged (P < .001). In addition, the expression of SP, CGRP and NKA in lung and brain tissue was reduced (P < .05). None of the animals in the four groups exhibited lung and brain parenchymal inflammation. The results from this study showed that SB705498 had a significant antitussive effect, could reduce the neurogenic inflammation by reducing the expression of SP, CGRP and NKA in a capsaicin-induced cough model of guinea pigs. The results further indicated that TRPV1 played an important role in UCC and SB705498 might be a promising therapeutic agent for UCC.

Prevalence of Arnold Nerve Reflex in Adults and Children With Chronic Cough

Cough originates from stimulation of structures innervated by the vagus nerve, including the airways and distal esophagus. Arnold nerve reflex describes the induction of cough by stimulation of the external auditory canal, which is innervated by the auricular branch of the vagus. Historically, the prevalence of this reflex has been reported in the range of 2%to 3%on the basis of studies of outpatients in otolaryngology practices, but has not been investigated in healthy volunteers or in patients with chronic cough. Two hundred adults and 100 children with chronic cough, as well as 100 adult and 100 pediatric volunteers, underwent evaluation consisting of stimulation of the external auditory canal of each ear with a cotton-tipped applicator. Cough occurring within 10 seconds of stimulation was considered induced by the intervention. Arnold nerve reflex was present in 25.5%of adults and 3%of children with chronic cough. The prevalence of the reflex was 2%among healthy adults and children. In adults with chronic cough, Arnold nerve reflex was observed more commonly in women (31.6%) than men (12.5%) and was unilateral in the majority of patients (90.2%). The greater than 12 fold prevalence of Arnold nerve reflex in adults with chronic cough compared with healthy volunteers supports the concept of cough hypersensitivity syndrome (CHS), in which vagal hypersensitivity is proposed to underlie chronic refractory cough. The absence of increased prevalence among children with chronic cough suggests that cough hypersensitivity syndrome is an acquired condition, perhaps triggered by viral respiratory infection or other environmental factor.

Agreement Among Radiographs, Fluoroscopy and Bronchoscopy in Documentation of Airway Collapse in Dogs

BackgroundAirway collapse is a common finding in dogs with chronic cough, yet the diagnosis can be difficult to confirm without specialty equipment.HypothesisBronchoscopic documentation of tracheobronchial collapse will show better agreement with fluoroscopic imaging than with standard radiography.AnimalsForty‐two dogs prospectively evaluated for chronic cough.MethodsIn this prospective study, three‐view thoracic radiographs were obtained followed by fluoroscopy during tidal respiration and fluoroscopy during induction of cough. Digital images were assessed for the presence or absence of collapse at the trachea and each lobar bronchus. Bronchoscopy was performed under general anesthesia for identification of tracheobronchial collapse at each lung segment. Agreement of imaging tests with bronchoscopy was evaluated along with sensitivity and specificity of imaging modalities as compared to bronchoscopy.ResultsAirway collapse was identified in 41/42 dogs via 1 or more testing modalities. Percent agreement between pairs of tests varied between 49 and 87% with poor–moderate agreement at most bronchial sites. Sensitivity for the detection of bronchoscopically identified collapse was highest for radiography at the trachea, left lobar bronchi, and the right middle bronchus, although specificity was relatively low. Detection of airway collapse was increased when fluoroscopy was performed after induction of cough compared to during tidal respiration.ConclusionsRadiography and fluoroscopy are complementary imaging techniques useful in the documentation of bronchial collapse in dogs. Confirming the presence or absence of tracheal or bronchial collapse can require multiple imaging modalities as well as bronchoscopy.

Fingerprint of Lung Fluid Ultrafine Particles, a Novel Marker of Acute Lung Inflammation

Background: Acute lung inflammation can be monitored by various biochemical readouts of bronchoalveolar lavage fluid (BALF). Objective: To analyze the BALF content of ultrafine particles (UFP; <100 nm) as an inflammatory biomarker in early diagnosis of acute and chronic lung diseases. Methods: Mice were exposed to different stress conditions and inflammatory insults (acute lipopolysaccharide inhalation, tobacco smoke and lethal dose of total body irradiation, i.e. 950 rad). After centrifugation, the cellular pellet was assessed while cytokines and ultrafine particles were measured in the soluble fraction of the BALF. Results: A characteristic UFP distribution with a D₅₀ (i.e. the dimension of the 50th UFP percentile) was shared by all tested mouse strains in the BALF of resting lungs. All tested inflammatory insults similarly shifted this size distribution, resulting in a unique UFP fingerprint with an averaged D₅₀ of 58.6 nm, compared with the mean UFP D₅₀ of 23.7 nm for resting BALF (p < 0.0001). This UFP profile was highly reproducible and independent of the intensity or duration of the inflammatory trigger. It returned to baseline after resolution of the inflammation. Neither total body irradiation nor induction of acute cough induced this fingerprint. Conclusions: The UFP fingerprint in the BALF of resting and inflamed lungs can serve as a binary biomarker of healthy and acutely inflamed lungs. This marker can be used as a novel readout for the onset of inflammatory lung diseases and for complete lung recovery from different insults.

Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs.

Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known.

Effect of viral upper respiratory tract infection on cough reflex sensitivity.

Acute viral upper respiratory tract infection (URI; common cold) is among the most common medical conditions affecting man, with cough being a typical feature of the associated syndrome. Studies employing capsaicin inhalation challenge to measure cough reflex sensitivity have demonstrated a transient tussive hyperresponsiveness induced by URI that reverts to normal by 4-8 weeks post infection. Mechanisms proposed to explain the induction of cough by URI include a number of infection-associated airway effects, such as enhanced release of cytokines, neurotransmitters, and leukotrienes; increased neural receptor levels; reduced activity of neutral endopeptidases; transient modulation of afferent neural activity; mucus hypersecretion; and, possibly, effects on cholinergic motor pathways. Recent studies evaluating urge-to-cough (UTC), the sensation of irritation preceding the motor act of coughing, have demonstrated that URI induces a transient enhancement of UTC analogous to the effect observed on cough reflex sensitivity. The recently introduced concept of the Cough Hypersensitivity Syndrome may provide an explanation for the commonly observed clinical phenomenon of acute viral URI triggering what will develop into chronic, refractory cough in a subgroup of patients.

Quantifying chronic cough: Objective versus subjective measurements

The assessment of chronic cough has been improved by the development of objective ambulatory cough monitoring systems and subjective quality of life questionnaires. Experimental induction of cough is a useful tool in the assessment of the cough reflex. We wanted to assess the reproducibility of and association between these measurements. This was a prospective observational study in patients with chronic cough of greater than 6 months' duration. All patients had an initial 24-h cough recording. They also completed a Leicester Cough Questionnaire, a Symptom Assessment Score, a Visual Analogue Score for cough and had a capsaicin cough challenge performed. They were reviewed at 8 weeks when all assessments were repeated. Twenty-five patients (15 women) with a mean age of 54 years were included in the study. The median cough count at the second visit (302) was significantly lower compared to the first visit (381, P < 0.01). However, the cough counts at both the visits correlated well (r = 0.9, P < 0.01). All the other forms of assessment were found to be highly reproducible at 8 weeks (r = 0.6-0.9, P < 0.01). Cough counts correlated well with the other forms of assessment (r = 0.4-0.6, P < 0.01). There was good correlation between each of the subjective forms of assessment (r = 0.6, P < 0.01). The various forms of assessment of cough are reproducible. Cough counting correlates well with subjective assessment of cough and cough reflex sensitivity. It appears to lie between these latter two assessments of cough and may represent the best global objective synthesis of cough.

Mechanical induction of cough in Idiopathic Pulmonary Fibrosis

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) frequently develop a dry, irritating cough which often proves refractory to anti-tussive therapies. The precise pathogenetic mechanisms responsible for this cough are unknown. We hypothesised that changes in nerves modulating mechanical sensitivity in areas of interstitial fibrosis might lead to enhanced cough response to mechanical stimulation of the chest in IPF.MethodsWe studied 27 non-smoking subjects with IPF (63% male), mean (SD) age 71.7 (7) years and 30 healthy non-smokers. Quality of life (Leicester Cough Questionnaire), cough symptom scores and cough severity scores (visual analog scales) were recorded. Percussion stimulation was applied over the posterior lung base, upper anterior chest and manubrium sternum at sequential frequencies (20 Hertz (Hz), 40 Hz and 60 Hz) for up to 60 seconds and repeated twice at two minute intervals. The number of subjects achieving two and five-cough responses, total cough counts and cough latency were recorded. In separate experiments, the effect of mechanical stimulation on the pattern of breathing was determined in eight IPF subjects and five control subjects.ResultsIn patients with IPF, we demonstrated strong correlations between subjective cough measurements, particularly the cough symptom score and Leicester Cough Questionnaire (r = -0.86; p < 0.001). Mechanical percussion induced a true cough reflex in 23/27 (85%) IPF subjects, but only 5/30 (17%) controls (p < 0.001). More patients with IPF reached the two-cough response at a lower frequency (20 Hz) posteriorly than at other positions. Highest mean cough totals were seen with stimulation at or above 40 Hz. Mechanical stimulation had no effect on respiratory rate but increased tidal volume in four (50%) subjects with IPF, particularly at higher frequencies. It was associated with increased urge to cough followed by a true cough reflex.ConclusionsThis study demonstrates that patients with IPF show enhanced cough reflex sensitivity to mechanical stimulation of the chest wall whilst normal individuals show little or no response. The observation that low frequency stimulation over the lung base, where fibrosis is most extensive, induces cough in more patients than at other sites supports the hypothesis that lung distortion contributes to the pathogenesis of cough in IPF.

Leser fragen – Experten antworten – Hustenreiz nach intravenöser Applikation von Opioiden

The (intravenous) administration of opioids is frequently associated with the induction of cough. This phenomenon is usually neither harmful for the patient nor bothersome. However, in some situations a severe cough may interfere with imaging, diagnostic or therapeutic procedures and thus, anesthesiologists may want to know effective preventive measures. The existing literature is extremely diverse and the results of clinical trials are sometimes conflicting. Based on experimental investigations in accordance with clinical findings this systematic review of the existing evidence helps to guide the management strategy if opioid induced cough should be avoided. Promising strategies - among others - in order to achieve this aim consist for instance of decreasing the injection speed in conjunction with pre-administration of lidocaine or clonidine.

Use of within-group designs to test anti-tussive drugs in conscious guinea-pigs

Introduction Cough is a common medical problem for which there are few effective drug treatments. A limited understanding of the mechanisms of induction and maintenance of cough and a paucity of suitable animal models frustrate drug discovery efforts to find novel anti-tussives. As in humans, guinea-pigs evoke a cough reflex upon exposure to tussive agents such as citric acid and capsaicin; both of which have been widely used to assess novel anti-tussive drugs. However, the potential for using within-group designs in drug development has received little attention and such designs may offer a way of assisting the drug discovery effort in the area of cough as well as other areas. Methods Cough can be monitored in conscious guinea-pigs by placing animals in a Perspex chamber, in which air is continually exchanged by use of negative pressure and drug delivery of aerosols to the chamber can be accurately timed. Cough in response to a tussive agent (e.g. 0.2–0.4 M citric acid; 10–30 μM capsaicin) is detected by the simultaneous microphonic recording of audible signals characteristic of the cough response as well as by positive pressure changes in the chamber generated by a cough dependent rapid expiration of air from the lungs. Both the sound and pressure signals are recorded using an online analyzer, whilst the number of coughs can be analyzed off-line. The number of coughs over a 15 min period is used to quantitate tussive events. Results Reproducible cough can be detected in animals using cross-over designs that lend themselves to drug studies. Both the time and concentration dependence of anti-tussive drug action can be evaluated in the same animal. Furthermore, the effect of different anti-tussive drugs can be evaluated thereby reducing between group error and thereby improving the sensitivity of the test. Discussion Repeated measures design improves the precision with which to evaluate anti-tussive drugs in preclinical models and could be used to make the drug discovery process more efficient.

Can aliskiren reduce the incidence of cough caused by ramipril?

reported results from a double-blind, multi-centre trial in which 837 patients with diabetes mellitus and hypertension were randomised to once-daily aliskiren (150 mg titrated to 300 mg after four weeks; n=282), ramipril (5 mg titrated to 10 mg; n=278) or the combination of aliskiren and ramipril for eight weeks. We are not commenting on the effects on blood pressures. We noticed that aliskiren significantly reduced plasma renin activity as monotherapy (by 66%) or in combination with ramipril (by 48%), despite large increases in plasma renin concentration in all treatment groups. Of particular interest was the reported rate of cough; 4.7% in patients receiving ramipril, but only 1.8% of patients receiving the aliskiren/ramipril combination and 2.1% of patients receiving aliskiren only. Although the difference between ramipril and combined ramipril/ aliskiren groups did not achieve significance (p=0.08), the authors noticed the possibility that aliskiren might reduce the incidence of angiotensinconverting enzyme (ACE) inhibitor-induced cough, a property of potential therapeutic value. No explanation for a possible mechanism by which aliskiren might reduce the incidence of ACE inhibitor-induced cough was presented. We would like to offer a theoretical explanation. Induction of cough by ACE inhibitors is believed to be linked to increased tissue accumulation of mainly bradykinin and possibly of other autacoids. ACE both generates angiotensin II from angiotensin I and degrades bradykinin. No ACE inhibitor can cause complete ACE inhibition, but there will always be some ‘escape’ from the inhibitory action. Aliskiren treatment is known to reduce plasma renin activity and plasma concentrations of angiotensin I, a major substrate of ACE. This would leave more active sites of ACE free to cleave bradykinin, which in turn would lead to less accumulation of bradykinin and to – less cough. Future studies will show whether aliskiren or other renin inhibitors may indeed reduce the incidence of cough in patients treated with ACE inhibitors. If true, this would offer possible advantages of combined drug treatment.

A simple noninvasive method to measure the cough reflex in dogs

Introduction: This study describes a method to measure the cough reflex in dogs that is simple to perform, requires no surgical intervention, and can be used to profile efficacy and side effect liabilities of antitussive drugs. Methods: Experiments were performed in propofol-anesthetized dogs in which cardiopulmonary functions were noninvasively monitored before and after the induction of cough produced by spraying 0.75 ml of distilled water into the trachea. Results: The magnitude of the cough response, measured by the frequency and amplitude, was not different for individual dogs performed with repeated trials on different days. Treatment with the opioid antitussive drug, torbutrol (0.055–0.0055 mg/kg sc), inhibited the cough frequency but not the amplitude induced by the water challenge. Furthermore, side effects of torbutrol were identified as mild respiratory depression and an anesthetic-sparing effect with propofol. Discussion: This method offers many distinct advantages to evaluate efficacy of antitussive drugs including the fact that no surgery is required, it takes only 15–20 min to complete an experiment, and it can be used to simultaneously profile antitussive and side effect liabilities of drugs developed for the treatment of cough.

Aerosol-Induced Sputum: An Effective, Inexpensive Method for Nebulization of a Super-Heated Mixture of 40 per cent Propylene Glycol in Isotonic Saline

An inexpensive device was used to provide a super-heated aerosol of a solution of 40 per cent propylene glycol in isotonic saline for sputum induction in 200 hospitalized patients. Seventy-three patients (Group I) had little or no spontaneous cough, 89 (Group II) had a dry, unproductive cough and 38 patients (Group III) had a productive cough prior to aerosol exposure. Fifty-six (76.7 per cent) in Group I, 71 (79.8 per cent) in Group II and all 38 patients in Group III produced an adequate sputum sample after one aerosol inhalation. Thirteen (17.8 per cent) in Group I and 15 (16.9 per cent) in Group II required two exposures, while only four (5.5 per cent) in Group I and three (3.3 per cent) in Group II needed three exposures to provide satisfactory specimens. Malignant cells were detected in the sputum of 61 (95.3 per cent) of 64 patients subsequently proven histologically to have bronchogenic carcinoma. These data and the lack of adverse effects encountered suggest the value of the apparatus described for induction of cough and sputum production in routine surveys for the early detection of carcinoma of the lung.