Changes in mechanics of breathing during experimental cough and sneeze in anaesthetized cats

Pleural pressure, airflow and tidal volume during experimental cough and sneeze elicited by mechanical stimulation of the tracheobronchial and nasal mucous membranes were investigated in fifty anaesthetized cats (pentobarbital, 40 mg/kg i.p.). Pressure-volume, pressure-flow and flow-volume relations were studied during these expulsive processes. In comparison to quiet breathing there was a decrease in dynamic lung compliance in both respiratory tract reflexes (p less than 0.001), especially in their expiratory phases. As compared to quiet breathing, the total work of breathing was significantly increased (p less than 0.001) in cough (20 times) as well as in sneeze (13 times). The total lung resistance increased markedly (p less than 0.001) in both cough and sneeze compared to quiet breathing. In these expulsive processes there was also a high "cough index" (resistance calculated from the peak flow and instantaneous pressure). The flow-volume curve in cough, in contradistinction to sneeze, indicated a significantly reduced airflow of the end of expiration (at 85% of the expired volume), demonstrating a concomitant bronchoconstriction.     

A New Methodology for Studying Dynamics of Aerosol Particles in Sneeze and Cough Using a Digital High-Vision,High-Speed Video System and Vector Analyses

Microbial pathogens of respiratory infectious diseases are often transmitted through particles in sneeze and cough. Therefore, understanding the particle movement is important for infection control. Images of a sneeze induced by nasal cavity stimulation by healthy adult volunteers, were taken by a digital high-vision, high-speed video system equipped with a computer system and treated as a research model. The obtained images were enhanced electronically, converted to digital images every 1/300 s, and subjected to vector analysis of the bioparticles contained in the whole sneeze cloud using automatic image processing software. The initial velocity of the particles or their clusters in the sneeze was greater than 6 m/s, but decreased as the particles moved forward; the momentums of the particles seemed to be lost by 0.15–0.20 s and started a diffusion movement. An approximate equation of a function of elapsed time for their velocity was obtained from the vector analysis to represent the dynamics of the front-line particles. This methodology was also applied for a cough. Microclouds contained in a smoke exhaled with a voluntary cough by a volunteer after smoking one breath of cigarette, were traced as the visible, aerodynamic surrogates for invisible bioparticles of cough. The smoke cough microclouds had an initial velocity greater than 5 m/s. The fastest microclouds were located at the forefront of cloud mass that moving forward; however, their velocity clearly decreased after 0.05 s and they began to diffuse in the environmental airflow. The maximum direct reaches of the particles and microclouds driven by sneezing and coughing unaffected by environmental airflows were estimated by calculations using the obtained equations to be about 84 cm and 30 cm from the mouth, respectively, both achieved in about 0.2 s, suggesting that data relating to the dynamics of sneeze and cough became available by calculation.     

Qualitative real-time schlieren and shadowgraph imaging of human exhaled airflows: an aid to aerosol infection control

Using a newly constructed airflow imaging system, airflow patterns were visualized that were associated with common, everyday respiratory activities (e.g. breathing, talking, laughing, whistling). The effectiveness of various interventions (e.g. putting hands and tissues across the mouth and nose) to reduce the potential transmission of airborne infection, whilst coughing and sneezing, were also investigated. From the digital video footage recorded, it was seen that both coughing and sneezing are relatively poorly contained by commonly used configurations of single-handed shielding maneuvers. Only some but not all of the forward momentum of the cough and sneeze puffs are curtailed with various hand techniques, and the remaining momentum is disseminated in a large puff in the immediate vicinity of the cougher, which may still act as a nearby source of infection. The use of a tissue (in this case, 4-ply, opened and ready in the hand) proved to be surprisingly effective, though the effectiveness of this depends on the tissue remaining intact and not ripping apart. Interestingly, the use of a novel 'coughcatcher' device appears to be relatively effective in containing coughs and sneezes. One aspect that became evident during the experimental procedures was that the effectiveness of all of these barrier interventions is very much dependent on the speed with which the user can put them into position to cover the mouth and nose effectively.From these qualitative schlieren and shadowgraph imaging experiments, it is clear that making some effort to contain one's cough or sneeze puffs is worthwhile. Obviously, there will be a large amount of variation between individuals in the exact hand or tissue (the most common methods) configuration used for this and other practical factors may hinder such maneuvers in daily life, for example, when carrying shopping bags or managing young children.     

Recognizing flu-like symptoms from videos

Background

Vision-based surveillance and monitoring is a potential alternative for early detection of respiratory disease outbreaks in urban areas complementing molecular diagnostics and hospital and doctor visit-based alert systems. Visible actions representing typical flu-like symptoms include sneeze and cough that are associated with changing patterns of hand to head distances, among others. The technical difficulties lie in the high complexity and large variation of those actions as well as numerous similar background actions such as scratching head, cell phone use, eating, drinking and so on.

Results

In this paper, we make a first attempt at the challenging problem of recognizing flu-like symptoms from videos. Since there was no related dataset available, we created a new public health dataset for action recognition that includes two major flu-like symptom related actions (sneeze and cough) and a number of background actions. We also developed a suitable novel algorithm by introducing two types of Action Matching Kernels, where both types aim to integrate two aspects of local features, namely the space-time layout and the Bag-of-Words representations. In particular, we show that the Pyramid Match Kernel and Spatial Pyramid Matching are both special cases of our proposed kernels. Besides experimenting on standard testbed, the proposed algorithm is evaluated also on the new sneeze and cough set. Empirically, we observe that our approach achieves competitive performance compared to the state-of-the-arts, while recognition on the new public health dataset is shown to be a non-trivial task even with simple single person unobstructed view.

Conclusions

Our sneeze and cough video dataset and newly developed action recognition algorithm is the first of its kind and aims to kick-start the field of action recognition of flu-like symptoms from videos. It will be challenging but necessary in future developments to consider more complex real-life scenario of detecting these actions simultaneously from multiple persons in possibly crowded environments.     

Activity of bulbar respiratory neurones during cough and other respiratory tract reflexes in cats

Changes evoked by mechanical stimulation of the relevant parts of the respiratory tract in the activity of inspiratory and expiratory neurones in the ventral respiratory group of the medulla oblongata, and in pleural pressure and the diaphragmatic electromyogram, were determined during cough, sneeze and the aspiration and expiration reflexes in 17 anaesthetized (but not paralysed) cats. The results of 72 tests of elicitation of the given reflexes showed that: Compared with the control inspiration, both the mean and the maximum discharge frequency of spontaneously active inspiratory neurones rose during the inspiratory phase of cough, sneeze and the aspiration reflex. Regular recruitment of new inspiratory units was also observed in the inspiratory phase of cough and the aspiration reflex. Compared with the control expiration, both the mean and the maximum discharge frequency of spontaneously active expiratory neurones rose during the cough, sneeze and expiration reflex effort. Recruitment of latent expiratory neurones was always observed in the expulsive phase of the given respiratory processes. The recruitment of latent expiratory neurones was accompanied by reciprocal inhibition of the activity of inspiratory units and recruitment of latent inspiratory neurones by inhibition of the activity of expiratory units and recruitment of latent inspiratory neurones by inhibition of the activity of expiratory units. Regular recruitment of the same expiratory neurones in all expulsive respiratory processes, together with the similar incidence of inspiratory neurones in the inspiratory phase of sneeze and the aspiration reflex, indicates that they are "nonspecific" in character.     

Effects of airway inflammation on cough response in the guinea pig

We have developed a guinea pig model for coughrelated to allergic airway inflammation. Unanesthetized animals wereexposed to capsaicin aerosols for 10 min, and cough frequency wascounted during this period. The cough evaluation was performed by the following three methods: visual observation, acoustic analysis, andmonitoring of pressure changes in the body chamber. These analysesclearly differentiated a cough from a sneeze. To elucidate therelationship between cough response and airway inflammation, animalswere immunosensitized and multiple challenged. Sensitized guinea pigspresented no specific changes microscopically, but multiple-challengedanimals showed an increased infiltration of inflammatory cells into theairway. Cough number in response to capsaicin increased significantlyfrom 4.7 ± 1.4 coughs/10 min in normal animals to 10.6 ± 2.0 coughs/10 min in sensitized animals and further to 22.8 ± 1.3 coughs/10 min in multiple-challenged animals. This augmentedcough frequency was significantly inhibited by the inhalation oftachykinin-receptor antagonists and by oral ingestion, but notinhalation, of codeine phosphate. The results suggest that airwayinflammation potentiates an elevation of cough sensitivity in this model.

     

Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations.     

Models of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations.     

GABA-ergic mechanisms in the central control of cough

The antitussive activity of gabalinoleamide (Gabalid U CB) was studied in 40 non-anaesthetized cats. The antitussive action of the substance was compared to that of codeine (Codein Spofa). Cough was induced by mechanical stimulation using a chronic tracheal cannula. Single cough parameters were evaluated from changes in the side tracheal pressure. When gabalinoleamide was administered in a dose of 100 mg/kg b.w. intramuscularly all the studied parameters of cough showed a statistically significant decrease, only the intensity of maximum cough effort remained unaffected. Gabalinoleamide administered in the same dose induced a statistically significant decrease of respiratory frequency and breathing amplitude, and prolonged the cycle of breathing by delaying the expiratory phase. Higher doses (200 and 300 mg/kg b.w.) did not have an increased cough suppressing effect. The quality and quantity of cough parameters were similar after codeine and gabalinoleamide.     

Airflow dynamics of coughing in healthy human volunteers by shadowgraph imaging: an aid to aerosol infection control

Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1-10), their maximum detectable cough propagation distances ranged from 0.16-0.55 m, with maximum derived velocities of 2.2-5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010-0.11 m(2), with maximum derived expansion rates of 0.15-0.55 m(2)/s. For the 10 males (cases 11-20), their maximum detectable cough propagation distances ranged from 0.31-0.64 m, with maximum derived velocities of 3.2-14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04-0.14 m(2), with maximum derived expansion rates of 0.25-1.4 m(2)/s. These peak velocities were measured when the visibility of the exhaled airflows was optimal and compare favorably with those reported previously using other methods, and may be seen as a validation of these previous approaches in a more natural setting. However, the propagation distances can only represent a lower limit due to the inability of the shadowgraph method to visualize these cough airflows once their temperature cools to that of the ambient air, which is an important limitation of this methodology. The qualitative high-speed video footage of these volunteers coughing into their sleeves demonstrates that although this method rarely completely blocks the cough airflow, it decelerates, splits and redirects the airflow, eventually reducing its propagation. The effectiveness of this intervention depends on optimum positioning of the arm over the nose and mouth during coughing, though unsightly stains on sleeves may make it unacceptable to some.     

Volitional control of reflex cough

Multiple studies suggest a role for the cerebral cortex in the generation of reflex cough in awake humans. Reflex cough is preceded by detection of an urge to cough; strokes specifically within the cerebral cortex can affect parameters of reflex cough, and reflex cough can be voluntarily suppressed. However, it is not known to what extent healthy, awake humans can volitionally modulate the cough reflex, aside from suppression. The aims of this study were to determine whether conscious humans can volitionally modify their reflexive cough and, if so, to determine what parameters of the cough waveform and corresponding muscle activity can be modified. Twenty adults (18-40 yr, 4 men) volunteered for study participation and gave verbal and written informed consent. Participants were seated and outfitted with a facemask and pneumotacograph, and two surface EMG electrodes were positioned over expiratory muscles. Capsaicin (200 μM) was delivered via dosimeter and one-way (inspiratory) valve attached to a side port between the facemask and pneumotachograph. Cough airflow and surface EMG activity were recorded across tasks including 1) baseline, 2) small cough (cough smaller or softer than normal), 3) long cough (cough longer or louder than normal), and 4) not cough (alternative behavior). All participants coughed in response to 200 μM capsaicin and were able to modify the cough. Variables exhibiting changes include those related to the peak airflow during the expiratory phase. Results demonstrate that it is possible to volitionally modify cough motor output characteristics.     

Transient Receptor Potential Ankyrin 1 Receptor Activation In Vitro and In Vivo by Pro-tussive Agents: GRC 17536 as a Promising Anti-Tussive Therapeutic

Cough is a protective reflex action that helps clear the respiratory tract which is continuously exposed to airborne environmental irritants. However, chronic cough presents itself as a disease in its own right and despite its global occurrence; the molecular mechanisms responsible for cough are not completely understood. Transient receptor potential ankyrin1 (TRPA1) is robustly expressed in the neuronal as well as non-neuronal cells of the respiratory tract and is a sensor of a wide range of environmental irritants. It is fast getting acceptance as a key biological sensor of a variety of pro-tussive agents often implicated in miscellaneous chronic cough conditions. In the present study, we demonstrate in vitro direct functional activation of TRPA1 receptor by citric acid which is routinely used to evoke cough in preclinical and clinical studies. We also show for the first time that a potent and selective TRPA1 antagonist GRC 17536 inhibits citric acid induced cellular Ca⁺² influx in TRPA1 expressing cells and the citric acid induced cough response in guinea pigs. Hence our data provides a mechanistic link between TRPA1 receptor activation in vitro and cough response induced in vivo by citric acid. Furthermore, we also show evidence for TRPA1 activation in vitro by the TLR4, TLR7 and TLR8 ligands which are implicated in bacterial/respiratory virus pathogenesis often resulting in chronic cough. In conclusion, this study highlights the potential utility of TRPA1 antagonist such as GRC 17536 in the treatment of miscellaneous chronic cough conditions arising due to diverse causes but commonly driven via TRPA1.     

Detection of Mouse Cough Based on Sound Monitoring and Respiratory Airflow Waveforms

Detection for cough in mice has never yielded clearly audible sounds, so there is still a great deal of debates as to whether mice can cough in response to tussive stimuli. Here we introduce an approach for detection of mouse cough based on sound monitoring and airflow signals. 40 Female BALB/c mice were pretreated with normal saline, codeine, capasazepine or desensitized with capsaicin. Single mouse was put in a plethysmograph, exposed to aerosolized 100 µmol/L capsaicin for 3 min, followed by continuous observation for 3 min. Airflow signals of total 6 min were recorded and analyzed to detect coughs. Simultaneously, mouse cough sounds were sensed by a mini-microphone, monitored manually by an operator. When manual and automatic detection coincided, the cough was positively identified. Sound and sound waveforms were also recorded and filtered for further analysis. Body movements were observed by operator. Manual versus automated counts were compared. Seven types of airflow signals were identified by integrating manual and automated monitoring. Observation of mouse movements and analysis of sound waveforms alone did not produce meaningful data. Mouse cough numbers decreased significantly after all above drugs treatment. The Bland-Altman and consistency analysis between automatic and manual counts was 0.968 and 0.956. The study suggests that the mouse is able to present with cough, which could be detected by sound monitoring and respiratory airflow waveform changes.     

CYTOLOGY OF THE POSTNASAL DRIP

About half of a series of 100 consecutive patients with disturbances of the eyes, ears, nose or throat complained of postnasal drip. When smears of the mucous discharge were examined it was found that in about a third of the cases in which there was complaint of drip, neither eosinophils nor neutrophils could be demonstrated. This indicates that causes of the drip other than allergic disease and infection must be considered.Cytologic examination of the postnasal drip showed that about one-third of the patients with nasal disease or histories positive for allergic reaction had nasal eosinophilia. Nasal eosinophilia was noted occasionally in patients with normal-appearing nasal structures and in patients with no history of allergic disease.     

Endotracheal Intubation in Mice via Direct Laryngoscopy Using an Otoscope

Mice, both wildtype and transgenic, are the principal mammalian model in biomedical research currently. Intubation and mechanical ventilation are necessary for whole animal experiments that require surgery under deep anesthesia or measurements of lung function. Tracheostomy has been the standard for intubating the airway in these mice to allow mechanical ventilation. Orotracheal intubation has been reported but has not been successfully used in many studies because of the substantial technical difficulty or a requirement for highly specialized and expensive equipment. Here we report a technique of direct laryngoscopy using an otoscope fitted with a 2.0 mm speculum and using a 20 G intravenous catheter as an endotracheal tube. We have used this technique extensively and reliably to intubate and conduct accurate assessments of lung function in mice. This technique has proven safe, with essentially no animal loss in experienced hands. Moreover, this technique can be used for repeated studies of mice in chronic models.     

Volume-timing relationships during cough and resistive loading in the cat.

The relationship between pulmonary volume-related feedback and inspiratory (CTI) and expiratory (CTE) phase durations during cough was determined. Cough was produced in anesthetized cats by mechanical stimulation of the intrathoracic tracheal lumen. During eupnea, the animals were exposed to single-breath inspiratory and expiratory resistive loads. Cough was associated with large increases in inspiratory volume (VI) and expiratory volume (VE) but no change in phase durations compared with eupnea. There was no relationship between VI and CTI during coughing. A linear relationship with a negative slope existed between VI and eupneic inspiratory time during control and inspiratory resistive loading trials. There was no relationship between VE and CTE during all coughs. However, when the first cough in a series or a single cough was analyzed, the VE/CTE relationship had a positive slope. A linear relationship with a negative slope existed between VE and eupneic expiratory time during control and expiratory resistive loading trials. These results support separate ventilatory pattern regulation during cough that does not include modulation of phase durations by pulmonary volume-related feedback.     

Influence of central antitussive drugs on the cough motor pattern.

The present study was conducted to determine the effects of administration of centrally active antitussive drugs on the cough motor pattern. Electromyograms of diaphragm and rectus abdominis muscles were recorded in anesthetized, spontaneously breathing cats. Cough was produced by mechanical stimulation of the intrathoracic trachea. Centrally acting drugs administered included codeine, morphine, dextromethorphan, baclofen, CP-99,994, and SR-48,968. Intravertebral artery administration of all drugs reduced cough number (number of coughs per stimulus trial) and rectus abdominis burst amplitude in a dose-dependent manner. Codeine, dextromethorphan, CP-99,994, SR-48,968, and baclofen had no effect on cough cycle timing (CTtot) or diaphragm amplitude during cough, even at doses that inhibited cough number by 80-90%. Morphine lengthened CTtot and inhibited diaphragm amplitude during cough, but these effects were not dose dependent. Only CP-99,994 altered the eupneic respiratory pattern. Central antitussive drugs primarily suppress cough by inhibition of expiratory motor drive and cough number. CTtot and inspiratory motor drive are relatively insensitive to the effects of these drugs. CTtot can be controlled independently from cough number.     

Markedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase-5

Chronic inflammatory and neuropathic pain is often difficult to manage using conventional remedies. The underlying mechanisms and therapeutic strategies required for the management of chronic pain need to be urgently established. The cyclic AMP (cAMP) second messenger system has been implicated in the mechanism of nociception, and the inhibition of the cAMP pathway by blocking the activities of adenylyl cyclase (AC) and protein kinase A has been found to prevent chronic pain in animal models. However, little is known regarding which of the 10 known isoforms of AC are involved in nociceptive pathways. Therefore, we investigated the potential pronociceptive function of AC5 in nociception using recently developed AC5 knockout mice (AC5-/-). We found that AC5-/- mice show markedly attenuated pain-like responses in acute thermal and mechanical pain tests as compared with the wildtype control. Also, AC5-/- mice display hypoalgesic responses to inflammatory pain induced by subcutaneous formalin injection into hindpaws, and to non-inflammatory and inflammatory visceral pain induced by injecting magnesium sulfate or acetic acid into the abdomen. Moreover, AC5-/- mice show strongly suppressed mechanical and thermal allodynia in two nerve injury-induced neuropathic pain models. These results suggest that AC5 is essential for acute and chronic pain, and that AC5 knockout mice provide a useful model for the evaluation of the pathophysiological mechanisms of pain.     

How much does nasal cavity morphology matter? Patterns and rates of olfactory airflow in phyllostomid bats

The morphology of the nasal cavity in mammals with a good sense of smell includes features that are thought to improve olfactory airflow, such as a dorsal conduit that delivers odours quickly to the olfactory mucosa, an enlarged olfactory recess at the back of the airway, and a clear separation of the olfactory and respiratory regions of the nose. The link between these features and having a good sense of smell has been established by functional examinations of a handful of distantly related mammalian species. In this paper, we provide the first detailed examination of olfactory airflow in a group of closely related species that nevertheless vary in their sense of smell. We study six species of phyllostomid bats that have different airway morphologies and foraging ecologies, which have been linked to differences in olfactory ability or reliance. We hypothesize that differences in morphology correlate with differences in the patterns and rates of airflow, which in turn are consistent with dietary differences. To compare species, we make qualitative and quantitative comparisons of the patterns and rates of airflow through the olfactory region during both inhalation and exhalation across the six species. Contrary to our expectations, we find no clear differences among species in either the patterns of airflow through the airway or in rates of flow through the olfactory region. By and large, olfactory airflow seems to be conserved across species, suggesting that morphological differences appear to be driven by other mechanical demands on the snout, such as breathing and feeding. Olfactory ability may depend on other aspects of the system, such as the neurobiological processing of odours that work within the existing morphology imposed by other functional demands on the nasal cavity.     

Bronchial hyperreactivity in patients who cough after receiving angiotensin converting enzyme inhibitors

Angiotensin converting enzyme inhibitors cause cough in some patients, but the mechanism of this effect is not known. Six patients in whom these inhibitors had caused cough and a further two patients in whom they were suspected to have caused worsening of bronchial asthma were studied. Nine patients in whom angiotensin converting enzyme inhibitors had not been associated with cough served as controls. In the controls lung function and bronchial reactivity were measured once; for the study patients these and the cough index were measured twice before rechallenge for two weeks with an angiotensin enzyme inhibitor and once afterwards. Rechallenge with drug for two weeks caused a significant decrease in the mean concentration of histamine causing a 35% fall in airways conductance and a significant increase in the cough index. Patients with cough showed bronchial hyperactivity compared with the controls, which increased after rechallenge with the inhibitors.Cough associated with converting enzyme inhibitors may be a variant of the cough in asthma.