The Fontana paradoxical reflex?

This commentary describes the "deflation cough" caused by deep lung deflations. Deflation cough is a paradoxical reflex similar to that described by Henry Head in 1889 for lung inflations that probably is mediated by the same sensors and afferent fibers in the lungs and activated by gastroesophageal reflux. We discuss how this reflex must be self-limiting, the general role of paradoxical reflexes in the body, and the possible clinical significance of deflation cough.

Do sex and atopy influence cough outcome measurements in children?

BACKGROUND: Despite the commonality of cough and its burden, there are no published data on the relationship between atopy or sex on objectively measured cough frequency or subjective cough scores in children. In 202 children with and without cough, we determined the effect of sex and atopy on validated cough outcome measurements (cough receptor sensitivity [CRS], objective cough counts, and cough scores). We hypothesized that in contrast to adult data, sex does not influence cough outcome measures, and atopy is not a determinant of these cough measurements. METHODS: We combined data from four previous studies. Atopy (skin prick test), the concentration of capsaicin causing two and five or more coughs (C2 and C5, respectively), objectively measured cough frequency, and cough scores were determined and their relationship explored. The children's (93 girls, 109 boys) mean age was 10.6 years (SD 2.9), and 56% had atopy. RESULTS: In multivariate analysis, CRS was influenced by age (C2 coefficient, 5.9; P = .034; C5 coefficient, 29.1; P = .0001). Atopy and sex did not significantly influence any of the cough outcomes (cough counts, C2, C5, cough score) in control subjects and children with cough. CONCLUSIONS: Atopy does not influence important cough outcome measures in children with and without chronic cough. However, age, but not sex, influences CRS in children. Unlike adult data, sex does not affect objective counts or cough score in children with and without chronic cough. Studies on cough in children should be age matched, but matching for atopic status and sex is less important.

Basic poster discussion: summary.

Twelve posters were presented in the section on Basic Research. They were discussed in a session chaired by Paul Davenport (Gainesville, US) and Marian Kollarik (Boston, US), with each poster presenter first briefly describing his/her poster.

Voluntary and reflex cough: similarities and differences.

Cough is defensive airway reflex subjected to a high degree of cortical control. Not surprisingly, all cough motor patterns can be mimicked and reflex cough be inhibited up to complete suppression, at least to a certain extent. Reflex cough differentiates from other airway reflex responses for its characteristic 3-phase motor pattern, and such pattern is maintained when coughing is produced voluntarily. Despite these and some other similarities, voluntary and reflex cough differ in many important respects, suggesting different neural control of the respiratory and non-respiratory musculature implicated in the generation of the cough modalities. This paper focuses the motor features that differentiate voluntary and reflex cough efforts, and highlights the importance of functional assessment of coughing in the diagnostic workup of respiratory and extra-respiratory diseases affecting the production of voluntary and reflex cough.

Respiratory expulsive efforts evoked by maximal lung emptying.

BACKGROUND: Some patients exhibit cough-like expiratory efforts ("deflation cough") during slow vital capacity (SVC) and/or FVC maneuver. The cause and motor features of these expulsive efforts are unknown. METHODS: Of 1,720 consecutive patients, 43 displayed deflation cough during SVC or FVC, and 18 agreed to participate in additional examinations involving radiologic and clinical assessments. Variables of the motor pattern of deflation cough, as well as its intensity and frequency, were recorded by means of a pneumotachograph; the "integrated" surface abdominal electromyographic activity (IEMG) was recorded as well. On different occasions, participants were randomly administered either an antacid or salbutamol or matched placebos. Comparisons between deflation cough variables prior to and after drug administration were performed by means of the analysis of variance and post hoc tests. RESULTS: Fourteen patients (77.8%) were affected by a respiratory disease, and all of them also reported esophageal and/or extraesophageal symptom(s) of reflux. In control conditions, maximal lung emptying was consistently accompanied by the appearance of deflation cough. Peak IEMG and peak expiratory flow rates of deflation cough correlated (r = 0.53, P < .05). Inhaled agents had no effect. Antacid abolished deflation cough in 11 patients, reduced its frequency in four, and was ineffective in three. Matched placebo was significantly less effective. CONCLUSIONS: All patients with deflation cough present symptoms of gastroesophageal reflux; acidic reflux, possibly evoked by the efforts of lung emptying, may be the causative factor. Receptors sensitive to lung collapse may also contribute to deflation cough when antacid administration fails.

Desensitization of the cough reflex by exercise and voluntary isocapnic hyperpnea.

Little is known about the effects of exercise on the sensory and cognitive aspects of coughing evoked by inhalation of tussigenic agents. The threshold for the cough reflex induced by inhalation of increasing nebulizer outputs of ultrasonically nebulized distilled water (fog), an index of cough reflex sensitivity, was assessed in twelve healthy humans in control conditions, during exercise and during voluntary isocapnic hyperpnea (VIH) at the same ventilatory level as the exercise. The intensity of the urge to cough (UTC), a cognitive component of coughing, was recorded throughout the trials on a linear scale. The relationships between inhaled fog nebulizer outputs and the correspondingly evoked UTC values, an index of the perceptual magnitude of the UTC sensitivity, were also calculated. Cough appearance was always assessed audiovisually. At an exercise level of 80% of anaerobic threshold, the median cough threshold was increased from a control value of 0.73 to 2.22 ml/min (P<0.01), i.e., cough sensitivity was downregulated. With VIH, the threshold increased from 0.73 to 2.22 ml/min (P<0.01), a similar downregulation. With exercise and VIH compared with control, mean UTC values at cough threshold were unchanged, i.e., control, 3.83 cm; exercise, 3.12 cm; VIH, 4.08 cm. The relationship of the fog nebulizer output/UTC value was linear in control conditions and logarithmic during both exercise and VIH. The perception of the magnitude of the UTC seems to be influenced by signals or sensations arising from exercising limb and thoracic muscles and/or by higher nervous (cortical) mechanisms. The results indicate that the adjustments brought into action by exercise-induced or voluntary hyperpnea exert inhibitory influences on the sensory and cognitive components of fog-induced cough.

Semantics and types of cough.

The panel considered the different types of cough in terms of basic mechanisms and clinical manifestations; both experimentally and clinically cough could occur in single efforts and as 'bouts' or 'epochs'. There were different definitions of cough but, provided the definition used was clear, this did not seem to be a major concern. The methods available for determining the nature or type of clinical cough were discussed, in particular automated cough counting in the clinic and more sophisticated methods available in the laboratory. With regard to semantics, there has been great variation in the names used; this applies to nervous sensors for cough, to cough reflexes and epochs, to clinical names for cough, and to cough sounds. Some simplification and uniformity of nomenclature seemed desirable although, provided the use of a name was clear, little confusion probably existed. The panel felt that the cough nomenclature would evolve with time and would prove to be useful for investigators, clinicians and coughers.

Workshop--cough: exercise, speech and music.

Twelve distinguished scientists attended the workshop, heard three presentations, and took part in the discussions. Fontana first described his unpublished studies on cough in exercise and during hyperventilation with healthy subjects. Both activities depressed cough induced by inhalation of distilled water aerosol (fog). The possible mechanisms were discussed. Gibson then described the successful use of speech therapy to treat chronic cough, and discussed the possible mechanisms, centering on the role of the larynx and its neural control. A comparison was made with the ability of speech and laughter to precipitate cough. Widdicombe discussed the scanty literature on the effect of singing and playing wind instruments on cough, most of the evidence being anecdotal. In the discussion periods several matters for future study arose. It is usually not clear if the modulation of cough, its depression, enhancement or excitation, arose primarily at peripheral sites (reflexes from the airways), or at a cortical level, or both. Nor is it clear whether the same results would be obtained with provoked cough and with spontaneous cough. But all three aspects of 'behavioual' changes in cough sensitivity (exercise, speech and music) could be further explored, and current techniques should make this possible.

Lung afferent activity: implications for respiratory sensation.

Stimuli within the lung can cause the sensations of pain, ache, irritation and urge-to-cough. In general these are abolished or inhibited by vagal section or vagal anaesthesia, or local anaesthesia within the airways. They are present in patients with functional high cervical spinal cord transaction and after general neuromuscular paralysis. There are at least nine sensors in the bronchopulmonary system, studied almost entirely in animals. It is at present impossible to link any one sensor with any one pattern of sensation. It is reasonable to suppose that urge-to-cough arises from sensors what mediate cough, but there are at least five sensors involved in this reflex, and how they relate to unpleasant sensation is unknown. The problem is that sensation can almost only be studied in humans, and the vagal neural mechanisms almost only in other species. Vagal sensors can also ameliorate the sensation of air hunger, and this is probably due to the action of slowly adapting pulmonary stretch receptors (SARs). The same sensors may give rise to the awareness of lung volume and its changes. Many sensors in the lungs can be sensitized or desensitized by natural or imposed conditions, and this could underlie the sensitization and desensitization of dyspnoeic sensations that have been described.

Intra-abdominal pressures during voluntary and reflex cough.

BACKGROUND: Involuntary coughing such as that evoked from the larynx, the laryngeal cough reflex (LCR), triggers a coordinated contraction of the thoracic, abdominal and pelvic muscles, which increases intra-abdominal pressure (IAP), displaces the diaphragm upwards and generates the expiratory force for cough and airway clearance. Changes in the IAP during voluntary cough (VC) and the LCR can be measured via a pressure catheter in the bladder. This study evaluated the physiological characteristics of IAP generated during VC and the LCR including peak and mean pressures and calculations of the area under the curve (AUC) values during the time of the cough event or epoch. METHODS: Eleven female subjects between the ages of 18 and 75 underwent standard urodynamic assessment with placement of an intravesicular catheter with a fiberoptic strain gauge pressure transducer. The bladder was filled with 200 ml of sterile water and IAP recordings were obtained with VC and the induced reflex cough test (RCT) using nebulized inhaled 20% tartaric acid to induce the LCR. IAP values were used to calculate the area under the curve (AUC) by the numerical integration of intravesicular pressure over time (cm H2O.s). RESULTS: The mean (+/- SEM) AUC values for VC and the LCR were 349.6 +/- 55.2 and 986.6 +/- 116.8 cm H2O.s (p < 0.01). The mean IAP values were 45.6 +/- 4.65 and 44.5 +/- 9.31 cm H2O (NS = .052), and the peak IAP values were 139.5 +/- 14.2 and 164.9 +/- 15.8 cm H2O (p = 0.07) for VC and LCR, respectively. CONCLUSION: The induced LCR is the involuntary rapid and repeated synchronous expiratory muscle activation that causes and sustains an elevated IAP over time, sufficient for airway protection. VC and LCR have different neurophysiological functions. Quantification of the LCR using AUC values and mean or peak IAP values may be useful as a clinical tool for determining neurophysiological airway protection status and provide a quantitative assessment of changes in a patient's functional recovery or decline.

Fog-induced cough with impaired respiratory sensation in congenital central hypoventilation syndrome.

RATIONALE: Congenital central hypoventilation syndrome (CCHS) is a genetic disorder mainly characterized by failure of automatic control of breathing, causing alveolar hypoventilation. Little is known regarding cough in CCHS. Parental reports indicate that patients cough normally during airway infections; however, previous studies have demonstrated no cough response to fog inhalation. OBJECTIVES: To evaluate the sensory and motor components of cough, respiratory sensations, and changes in ventilation evoked by fog inhalation in children with CCHS and in sex- and age-matched control subjects. METHODS: Cough threshold was measured and cough intensity was indexed in terms of cough peak expiratory flow and integrated abdominal electromyographic activity. The pattern of breathing was recorded by inductive plethysmography. Respiratory sensations were also investigated. MEASUREMENTS AND MAIN RESULTS: All control subjects and six of seven patients coughed in response to fog inhalation. The seventh coughed with citric acid aerosol inhalation. Cough threshold values were similar in control subjects (range, 0.40-2.22 ml/min) and patients (range, 0.40-3.26 ml/min). Mean values of cough peak expiratory flow and of integrated abdominal electromyographic activity-related variables during coughing were also similar and corresponded to 80% of those recorded during maximum voluntary cough. Cough appearance was preceded by respiratory sensations and increases (P < 0.01) in ventilation in the control subjects but not in the patients. CONCLUSIONS: Children with CCHS have normal cough threshold and motor responses to fog inhalation. However, the lack of respiratory sensations and the likely related ventilatory changes typically elicited by tussigenic fog concentrations suggest a neural sensory deficit that may increase the risk of respiratory disease in these patients.

What is cough and what should be measured?

Cough is usually defined as a three-phase event, although for convenience clinicians may prefer to define it as only the expiratory expulsive efforts. Cough may occur as a single event or as a cough 'epoch' (or 'bout' or 'attack') that includes several or many expiratory efforts in a single episode. The distinction between a single cough and a cough epoch is important, both in mechanistic and clinical implications, since the latter may include many 'expiration reflexes' (ERs), for which the functions and neural mechanisms are different from those of the cough reflex. We describe the various ways in which cough can be assessed. For simplicity in clinical work the main methods are patient scores or automated cough counters; these assess only one aspect of the complex changes in cough. For analytical and basic medical studies other facets of cough need to be included: expiratory EMGs, respiratory pressures, airflows and lung volume changes. Cough 'intensity', a much used expression, needs to be defined in terms of the facets of cough which are being measured.

Cough throughout life: children, adults and the senile.

We review cough from premature birth, mature neonatal life, in childhood and adult life, and in old age. There is a regrettable lack of definitive studies, but many clues in the literature. The cough reflex seems weak in premature infants, but develops with maturity. It is pronounced in childhood, but there seem to be no studies comparing its strength then with that in adulthood. In old age the cough may weaken, as indicated by the prevalence of aspiration pneumonia. These changes are presumably related to the development and degeneration of the afferent and central nervous pathways for cough, which may be reflected in the changes in laryngeal muscle function with age. There is much evidence that age influences the development of the respiratory system in general, and of the immune system which would affect the degree, frequency and clinical issues of cough. Other factors that limit our understanding of the changes in cough with age include the reporting of cough by parents in infants and carers in old age and the use of different diagnostic criteria throughout life. Age-related variation in cough sensitivity seems to be well established, but its quantitation and mechanisms require much further research.

Supramedullary influences on cough.

The evidence for supramedullary influences on cough is largely indirect. Cough can be voluntarily induced or inhibited, functions usually thought to reside in the cerebral cortex. A sensation of 'urge-to-cough' usually precedes cough due to an airway irritant stimulus, and this may well involve the cerebral cortex. In conditions with interruption of the pathways between the cortex and the brainstem, such as strokes and Parkinson's disease, voluntary cough may be inhibited without disruption of reflex cough from the larynx or lower airways. 'Habit cough', like Tourette's syndrome, is assumed to be cortically mediated. Placebos and many treatments based on complementary medicine are effective in inhibiting clinical cough, and the site of action is likely to be the cerebral cortex. In sleep and in anaesthesia cough is depressed and, again, this seems likely to be at a cortical level. However there are few or no experimental or clinical observation as to the localization and functions of supramedullary areas responsible for cough. It is a field of research wide open for exploration.