Functional organization of the central cough generation mechanism

Recent studies evaluating the effects of pulmonary afferents, chemoreceptors, and antitussive drugs on the cough motor pattern indicate that this reflex is regulated in a different manner than breathing. Furthermore, regulatory differences exist between tracheobronchial and laryngeal cough. We propose a functional model of the brainstem elements participating in the production of cough that accounts for these regulatory differences. The model incorporates known brainstem interneuronal pathways as well as novel regulatory elements for tracheobronchial and laryngeal cough. Each of these novel regulatory elements controls the excitability of a common motor pattern generation network. Given that cough and breathing are associated with profoundly different spatiotemporal alterations in motor drive to respiratory motoneurons, brainstem elements common to the generation of both behaviours must be capable of a high degree of plasticity.     

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.     

The use of multiscale systems biology approaches to facilitate understanding of complex control systems for airway protection

Airway protection is a critically important function that prevents/limits the intrusion of foreign material into the pulmonary tree. A host of different behaviors participate in this process. The control, coordination, and execution of these behaviors is a complex process that has recently received increased attention. Data from human clinical and animal studies support the concept of a coordinated neural control system that governs the appropriate expression and sequencing of airway protective behaviors. Our current knowledge of the proposed neural control network for breathing, cough, swallow and other airway protective behaviors indicates that it is a highly complex system that can 'rewire' (reconfigure) itself to perform several different functions. Computational modeling and simulation have been used as tools to investigate this system. The results of modeling efforts have yielded motor output patterns of upper airway and respiratory muscles that are very similar to those recorded in vivo. Regulation and coordination of multiple different airway protective behaviors have been successfully simulated. Outcomes of simulation efforts support the hypothesis that computational modeling of airway protection can yield important testable hypotheses regarding brainstem neural network functions and organization. Modeling of complex systems can be challenging but the open availability of straight-forward computational tools is likely to result in increased implementation of modeling and simulation as adjuncts to traditional methods of investigation of the control of the upper airway.     

Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons.

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expiratory muscle strength training in persons with multiple sclerosis having mild to moderate disability: effect on maximal expiratory pressure, pulmonary function, and maximal voluntary cough

OBJECTIVE: To determine the effect of expiratory muscle strength training (EMST) on maximal expiratory strength, pulmonary function, and maximal voluntary cough in persons with multiple sclerosis (MS) having mild to moderate disability. DESIGN: Before-after trial. SETTING: Assessments were completed in the privacy of the subject's home or exercise physiology laboratory. PARTICIPANTS: Seventeen persons with MS were age- and sex-matched to 14 healthy controls. INTERVENTION: Eight weeks of EMST and 4 weeks of detraining. MAIN OUTCOME MEASURES: Maximal respiratory pressures, pulmonary function, and maximal voluntary cough were assessed 3 times (pretraining, posttraining, detraining). Maximal expiratory pressure (MEP) was assessed weekly and training intensity adjusted based on the new measurement. RESULTS: Subjects with MS had lower MEP, decreased pulmonary function, and weaker maximal voluntary cough at each assessment. EMST increased MEP and peak expiratory flow. However, improvement in maximal voluntary cough only occurred in subjects with a moderate level of disability when the MS group was subdivided into mild and moderate disability levels based on the Expanded Disability Status Scale. CONCLUSIONS: EMST is a viable tool to enhance the strength of the respiratory muscles. However, further work is needed to determine the best parameters to assess change in cough following EMST.     

Augmented breath phase volume and timing relationships in the anesthetized rat

Augmented breaths (ABs), or sighs, are airway protective reflexes and part of the normal repertoire of respiratory behaviors. ABs consist of two phases, where phase I volume and timing resembles preceding eupnic breaths, and phase II is an augmenting motor pattern and occurs at the end of phase I. Recent evidence suggest multiple respiratory motor patterns can occur following dynamic functional reconfiguration of one respiratory neural network. It follows that the response of the respiratory network to modulatory inputs also may undergo dynamic reconfiguration. We hypothesized that lung-volume related feedback during ABs would alter AB timing differentially during phase I and II. We measured phase I and II volumes and durations in urethane anesthetized rats with decreased lung volume secondary to three models of varying phrenic motor impairment (spinal injury alone, unilateral phrenicotomy, and combined injuries). AB phase I and II inspired volume were decreased after phrenic motor impairment (p<0.05). In contrast, only phase I duration following injury was altered compared to controls. Phase II duration remaining unchanged despite the greatest effect of injury on volume occurring during phase II. Thus, sigh volume-timing relationships differ between phases of an augmented breath suggesting that the response of the respiratory network to modulatory inputs has changed. These data support the hypothesis that multiple respiratory behaviors occur following dynamic reconfiguration of the respiratory neural network.     

Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart

1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS)