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Objective: To implement subjective methods for measuring the impact of chronic cough on patients' daily life, including an Italian version of the symptom-specific, health status measure for patients with chronic cough, i.e. the Leicester Cough Questionnaire (LCQ)., Methods: Sixty-five chronic cough patients attended a tertiary cough clinic on two separate occasions 8 weeks apart. The visual analogue scale for cough severity (VAS), the LCQ and the cough disturbance score (CDS) were administered on both occasions. The LCQ was adapted for Italian conditions following a forward-backward translation procedure. Concurrent validation, internal consistency, repeatability and responsiveness were determined., Results: The CDS, VAS and LCQ were correlated (r coefficients ranging from 0.69 to 0.94, p < 0.01). The internal consistency for each LCQ domain was high (alpha coefficient range 0.87-0.93), as was the 8-week repeatability of the LCQ in the patients (n = 36, 60 %) who displayed no change in CDS and VAS (intra-class correlation coefficient = 0.86, p < 001) over the same period. Patients who reported an improvement in CDS and VAS after 8 weeks (n = 29) also demonstrated significant improvements in each LCQ domain. The mean difference in LCQ total score before and after improvements was 2.26 (95 % CI: 1.58-4.47)., Conclusions: The Italian version of the LCQ appears to be just as valid as the other language versions of the questionnaire. In addition, the CDS appears to be a clinically useful, symptom-specific measure of the overall disturbance provoked by cough., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In patients with chronic cough and age-matched control subjects, we attempted to evoke coughing and/or an urge to cough (UTC) by finger pressure along the sternocleidomastoid and sternum, on the lower cervical or first dorsal vertebrae, the jugular notch as well as with maximum neck extension and flexion These mechanical actions were ineffective in controls but reproducibly evoked coughing or UTC in about 50% of chronic coughers; sternal and spinal responses were abolished temporarily by local cooling. The results may disclose a novel paradigm of cough sensitisation possibly involving central convergence of somatic and visceral neural stimuli., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Chronic cough is a major health problem worldwide and patients are best managed in specialised tertiary centres. Little information is available on the characteristics of chronic cough patients in several European countries, including Italy., Aims: We report on the demographic, anthropometric and clinical features of a large Italian population of adult chronic cough outpatients (about 1200), who were referred to a specialised clinic in Florence, Italy, from 2008 to 2018., Methods: Demographic, environmental, lifestyle and clinical information was collected at enrolment by means of a custom-designed electronic questionnaire that only allowed for uniform responses. A subjective measure of cough-related discomfort (cough score) was also obtained using a modified Borg Scale. A multivariable logistic regression model was defined to identify the patients' characteristics associated with the cough score., Results: The characteristics of the examined population (n = 1204 outpatients) were strikingly similar to those described elsewhere. Female patients outnumbered the males [n = 847 females, (70.0%)]; both females and males displayed the same average cough score. The median age of outpatients was 61 (quartile 1 = 48; quartile 3 = 70) years; age and cough duration were unrelated to the cough score. Nasal obstruction, coughing during consultation, coughing during meals, throat clearing and the presence of respiratory abnormalities were correlated with the degree of discomfort caused by coughing., Discussion: The features of chronic cough patients are similar worldwide. The process of cough reflex hypersensitisation may soothe sex-related perceptual differences, leading to similar levels of discomfort., Conclusions: There seem to be clinical indicators that help in assessing the level of cough-related discomfort.

Idiopathic pulmonary fibrosis is a peripheral subpleural interstitial lung disorder limited to the lung not involving the airways. It has a poor prognosis (survival less than 5 years) and commonly an interstitial pneumonia radiological pattern. Patients complain of a chronic dry cough in 80% of cases. A cough is often the first symptom of this rare disease, preceding dyspnea by years, and is associated with a poor prognosis, high dyspnea scores and low FVC percentages. The pathogenetic mechanisms leading to coughing in IPF are unclear. This review focuses on recent evidence of cough pathophysiology in this disease. Gastroesophageal reflux may promote coughing in IPF patients; bile salts and pepsin may be abundant in BAL of these patients, inducing overproduction of TGF-β by airway epithelial cells and mesenchymal transition with fibroblast recruitment/activation and extracellular matrix deposition. Patients have an enhanced cough reflex to capsaicin and substance P with respect to control subjects. Moreover, patients with the MUC5B polymorphism show more severe coughing as MUC5B encodes for the dominant mucin in the honeycomb cysts of IPF patients. Comorbidities, including asthma, gastroesophageal reflux, hypersensitivity pneumonitis, bronchiectasis, chronic obstructive pulmonary disease and emphysema, can induce coughing in IPF patients. There is no clear explanation of the causes of coughing in IPF. Further research into the pathophysiology of IPF and the pathogenetic mechanisms of coughing is necessary to improve survival and quality of life.

Background: Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO 2 rebreathing test in patients with chronic cough of any origin., Methods: Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg levodropropizine, 15 mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93% oxygen and 7% CO 2 for 5 min. Fractional end-tidal CO 2 (Fetco 2 ) and inspiratory minute ventilation (V˙i) were continuously monitored. Changes in breathing pattern variables were also assessed., Results: At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia (P < .01). The ventilatory increases by hypercapnia were mainly accounted for by a rise in the volume components of the breathing pattern., Conclusions: The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO 2 may represent a useful tool to investigate the central respiratory effects of antitussive agents., Trial Registry: European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/., (Copyright © 2017. Published by Elsevier Inc.)

Background: Cough is a common presenting symptom in patients with idiopathic interstitial pneumonia (IIP); it is often disabling, and lacks effective treatment. Studies in animals suggest that carcainium chloride, a quaternary derivative of the local anesthetic lidocaine, is able to inhibit experimentally induced cough by a mechanism of action distinct from that of lidocaine., Objective: To determine the effectiveness of aerosolised carcainium chloride (VRP700) in controlling cough in patients with IIP., Methods: Eight female patients (mean age 71 years) with IIP were investigated in a double blind, randomised, placebo controlled crossover, adaptive contingency study design (EudraCT Number 2010-021350-19). The study consisted of a screening visit to assess the eligibility of patients, and two separated (48-72 h) study days. On the two study days, patients were randomised to receive either nebulized VRP700 (1.0 mg/kg) on the first study visit followed by nebulised placebo (sodium chloride 0.9%) on the second visit, or placebo on the first visit followed by VRP700 on the second visit. The primary endpoint was cough frequency over a 4-h assessment period; secondary endpoints were subjective cough-related level of discomfort as assessed by a visual analogue scale (VAS) and the subjective response to treatment as assessed by a quality of life question. Safety (ECG, spirometry, urine and blood tests) and adverse events occurring during the trial were also investigated., Results: In all patients both VRP700 and placebo decreased cough frequency; however, mean decreases in cough frequency after treatment with VRP700 were significantly (P < 0.001) higher than with placebo. Similarly, mean reductions in VAS score were significantly (P < 0.001) higher after treatment with VRP 700 compared with placebo. All but one patient indicated that they felt better after receiving VRP700. No adverse events were reported during the study, nor were any changes in ECG variables, spirometry, urine and blood tests noted., Conclusion: The results of this exploratory study indicate that nebulised VRP700 improved cough and quality of life in hospitalised IIP patients with no significant side effects. A larger trial is warranted to assess these promising results., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms., Methods: A total of 157 consecutive outpatients underwent DC assessment and 24-h multichannel intraluminal impedance pH (MII-pH) monitoring; 93/157 also had chronic cough. Patients performed two to four slow vital capacity maneuvers and DC was detected aurally. Subsequently, they underwent 24-h MII-pH monitoring, the outcomes of which were defined as abnormal when acid or non-acid reflux events were > 73., Results: DC occurred in 46/157 patients, 18 of whom had abnormal MII-pH outcomes; 28 of the remaining 111 patients without DC also had abnormal MII-pH findings. Thus, in the patients as a group, there was no association between DC and MII-pH outcomes. DC occurred in 40/93 of the chronic coughers; 15 of whom had acid reflux. All but 2 of the 53 patients without DC had normal MII-pH outcomes (P < .001), and the negative predictive value of DC for excluding acid reflux was 96.2%. At follow-up, 65% of coughers showed significant improvement after treatment., Conclusions: The overall prevalence of DC was 29%, increasing to 43% in chronic coughers in whom the absence of DC virtually excludes acid reflux. Therefore, DC assessment may represent a useful screening test for excluding acid reflux in chronic coughers with reflux symptoms., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Deflation cough (DC), i.e. the cough-like expiratory expulsive efforts evoked by maximal lung emptying, is partially inhibited by prior intake of an antacid. We wished to compare the effects of an anti-reflux medical device (Gastrotuss(®)) and of a widely used antacid drug (Maalox(®)) on the number of expiratory thrusts evoked by maximal lung emptying in chronic cough patients., Methods: Twenty consecutive chronic cough outpatients also presenting DC attended the clinic on three separate occasions and were requested to inhale to near total lung capacity and then exhale maximally for at least 6 s. Trained investigators detected aurally the number of cough efforts evoked by maximal lung emptying prior to and 1, 5, 10, 30 e 60 min after administration of either Maalox(®), or Gastrotuss(®) or placebo. The liking of the administered agents was also rated., Results: In control conditions, maximal lung emptying was consistently accompanied by the appearance of DC. The number of efforts was unchanged after placebo whereas it was markedly (P < 0.001) reduced 1-10 min following Maalox(®) and Gastrotuss(®) administration. The value of liking for Gastrotuss(®) was greater (P < 0.01) than those of Maalox(®) and placebo., Conclusions: Pre-treatment with anti-reflux agents with a substantially different composition are equally effective in inhibiting DC. The liking of the two compounds used in the present experiments differed considerably and may be important to improve adherence to treatment in patients undergoing long-term therapy for reflux-related symptoms., (Copyright © 2015. Published by Elsevier Ltd.)

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.

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.

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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The Workshop considered the mechanisms whereby the 'cough center' could be tuned by various afferent inputs. There were particular presentations on the effects of inputs from the nose, mouth, respiratory tract and lungs, cerebral cortex, somatic tissues and the pharynx. From all these sites cough induced from the lungs could be increased or decreased in its strength or modified in its pattern. Thus 'tuning' of cough could be due to the interaction of afferent inputs, or to the sensitization or desensitization of brainstem neural pathways. The pattern of response depended on the 'type' of cough being studied and, in some instances, on the timing of the sensory input into the brainstem. Cough inputs could also affect various 'non-cough' motor outputs from the brain, although this was not the main theme of the Workshop. The main conclusion was that cough is not a stereotyped output from the medullary 'cough center', but that its pattern and strength depend on many afferent inputs acting on the 'cough center'., (Copyright © 2011. Published by Elsevier Ltd.)

Background: Aspiration and respiratory tract infections are commonly observed in patients following conservative laryngeal surgery such as supracricoid laryngectomy with cricohyoidopexy (CHP). Since laryngeal closure is important for cough effectiveness, we hypothesised that CHP reduced cough intensity by affecting the cough motor pattern., Methods: In ten male patients with laryngeal cancer eligible for CHP, we assessed the intensity of maximum voluntary cough (MVC) prior to and 2 months after surgery. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGp) and the ratio of IEMGp to the duration of the expiratory ramp during cough (TEC), i.e. the rate of rise of IEMG activity (IEMGp/ TEC). For each cough effort, the duration of the compressive phase (CP), the cough peak flow (CPF), the time elapsed from the onset of cough to CPF (TTP) and their ratio, i.e. the volume acceleration (VA), were also evaluated., Results: CHP did not affect IEMG-related variables; in contrast, it reduced (p < 0.01) CPF, CP and lengthened (p < 0.05) TTP values. In consequence, cough VA values after CHP were consistently lower than in control condition., Conclusions: Supracricoid laryngectomy with CHP alters the intensity of voluntary cough as indexed by flow-related variables. This may reduce cough efficiency and facilitate the onset and/or persistence of chest infections (Tab. 2, Fig. 1, Ref. 22).

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.

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.

Airway receptors mediate cough and ventilatory adjustments. Simultaneous assessment of cough sensory-motor components and changes in breathing pattern may provide insights into the receptor(s) prevailingly stimulated by inhaled irritants. Nineteen subjects inhaled capsaicin and fog up to threshold concentrations for cough. Cough intensity, respiratory sensations and changes in breathing pattern induced by the two irritants were compared. Capsaicin and fog cough threshold values did not correlate. Coughing induced by both agents was preceded by qualitatively similar sensations and by significant increases in minute ventilation and respiratory drive due to selective increases in tidal volume (P<0.01). Cough intensity was similar with both agents. Cough frequency and the intensity of the urge to cough were higher with capsaicin (P<0.01). The lack of correlation between fog and capsaicin cough threshold values suggests differences in the neural mechanisms activated. The selective increase in tidal volume suggests prevailing involvement of rapidly adapting receptors. The stronger sensations evoked by capsaicin may contribute to the higher cough frequency observed with this agent.

Cough is a defensive airway mechanisms which involves the sequential activation of several laryngeal and respiratory muscles in the generation of the typical four-phase motor pattern. Activation of such muscles can be considered to represent the "primary" cough motor mechanism, and its functional significance, although complex, appears to be fairly well established. Nonetheless, the outflows of cough are numerous, and may additionally involve the reflex or mechanical activation of other respiratory and non-respiratory motor systems. These additional, or "secondary", outflows of cough can mainly be regarded as being involved in either enhancing the defensive function of cough, or opposing the possible noxious effects exerted by the mechanical stresses of coughing. In addition, both the primary and secondary cough motor mechanisms are known to play multiple functional roles, thus considerably complicating the cough panorama. Finally, some of the secondary cough motor responses, such as the changes in the pattern of breathing, seem to be devoid of any favourable action and their functional meaning, if any, is not fully understood. Although it is well known that all patterns of cough can be produced voluntarily, the extent to which also volitional cough is accompanied by an array of motor responses similar to that of reflex cough remains to be elucidated.

Congenital central hypoventilation syndrome (CCHS) is defined as failure of the chemical (autonomic) control of breathing causing alveolar hypoventilation in the absence of pulmonary, cardiac, neuromuscular or patent brainstem lesions. Hypoventilation is predominant in non-rapid-eye-movement sleep, during which breathing is primarily under chemical control. Failure of the central integration of chemosensory inputs is proposed as the putative defect. A genetic basis for CCHS is supported by lines of evidence. In some diseases of the central nervous system there is more or less complete depression of the cough reflex, whereas spontaneous ventilation is generally preserved. Little is known regarding cough in CCHS patients. Parents consistently report that their children cough 'normally' during airway infections; in contrast, experimental lines of evidence suggest that CCHS children lack a cough response following inhalation of a tussigenic agent. Although several factors may account for the discrepancy, the possibility of a weakened or even absent cough reflex remains to be fully ascertained. Conceivably, a defective cough reflex, in conjunction with the well established lack of perception of respiratory discomfort, might result in an increased risk of potentially serious respiratory complications in CCHS patients.

Inhalation of ultrasonically nebulised distilled water (fog) induces cough; however, the receptor type(s) mediating this reflex are poorly defined. In humans, cough threshold can be determined by inhalation of progressively increasing fog concentrations; the intensity of the associated motor response can be indexed in terms of flow-related variables as well as of the peak and slope of the integrated electromyographic activity of the abdominal muscles. We have evaluated coughing in patients with Parkinson's disease who show a high incidence of serious chest infections. These patients turned out to have a normal cough threshold but reduced expiratory muscle force during reflex coughing; this suggests an impairment in the central mechanisms subserving muscle activation possibly leading to inefficient airway clearing. Recurrent chest infections also affect laryngectomised patients. These patients have a normal cough threshold but reduced muscle force during coughing in response to threshold stimuli. Voluntary coughing is preserved in these patients, and this should be used to facilitate mucus removal. In normal subjects, fog inhalation causes cough and increases in respiratory drive and minute ventilation, mainly accounted for by increases in tidal volume, possibly due to activation of airway rapidly adapting receptors. Nedocromil sodium administration increases cough threshold and attenuates the ventilatory responses. The assessment of sensory and motor components of coughing may represent a useful tool for those investigating cough in humans., (Copyright 2002 Elsevier Science Ltd.)

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.

Ablation of the larynx implies withdrawal of afferent information from receptors involved both in the control of expiratory flow and in the genesis of protective airway reflexes including coughing. To investigate the effects of laryngectomy on the sensory and motor component of coughing, maximal voluntary cough (MVC) efforts as well as the reflex cough (RC) responses at threshold (T) and suprathreshold (1.8 x T, ST) levels induced by inhalation of progressively increasing concentrations of ultrasonically nebulized distilled water (fog) were analyzed in 10 laryngectomized patients and 10 control subjects. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGP) and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity (IEMGP/TEC). Cough peak flow was also recorded. Cough threshold was similar in patients and controls, as were IEMGP, TEC, and IEMGP/ TEC recorded during MVC and RCST. In contrast, during RCT, patients' IEMGP was significantly reduced (p < 0.05), thus leading to a significant decrease in IEMGP/TEC (p < 0.05) even in the absence of significant differences in TEC. Cough flow closely correlated with IEMG-related variables. Cough volume acceleration, i. e., the ratio of cough peak flow to the corresponding time to cough peak flow was also significantly reduced in the patients, especially during RCT (p < 0.01). The results suggest that the lack of signals arising from the larynx may result in a reduction of cough volume acceleration as well as in the intensity of abdominal muscle contractions during RCT. These factors may contribute to facilitate the onset and/or the persistence of chest infections in laryngectomized patients.

Cough-related variables such as cough frequency, time to onset (i.e. the time until the first cough occurs) and the cough index (i.e. the ratio between the cough frequency and the time to onset) may be important when interpreting results of cough challenges for therapeutic interventions or for comparative research purposes. Nevertheless, repeatability (or reproducibility) for these widely used variables has been poorly studied. In thirty normal subjects, coughing was induced by inhalation of threshold (T) and suprathreshold (1.6 x T) concentrations of ultrasonically nebulized distilled water (fog). Cough threshold was taken as the lowest fog concentration that evoked at least one cough effort during two challenges separated by a 30-min interval. During challenges performed at both threshold and suprathreshold stimulus intensity, cough frequency, time to onset, and the cough index were assessed; within-subject repeatability for these variables was subsequently evaluated. Median +/- interquartile range cough threshold value was 0.9+/-0.5 mL x min(-1). During the two challenges performed to assess cough threshold, the mean +/-SD values of cough frequency, time to onset, and cough index were similar (5.0+/-2.7 and 5.3+/-3.1 coughs x min(-1), 32.4+/-13.3 and 32.9+/-13.6 s, and 0.2+/-0.2 and 0.2+/-0.2, respectively). However, none of these cough-related variables proved to be sufficiently repeatable. During the two challenges performed at suprathreshold stimulus intensity, mean values of cough frequency, time to onset, and cough index were also similar (20.0+/-9.0 and 18.2+/-10.2 coughs x min(-1), 13.5+/-5.8 and 12.0+/-4.62 s, and 1.7+/-1.0 and 1.8+/-1.2); furthermore, all considered variable of suprathreshold challenge turned out to be reproducible. In conclusion, during fog challenges at threshold stimulus intensity, cough frequency, time to onset and cough index cannot reliably be used for evaluating cough responses. However, these cough-related variables may represent useful and reliable research tools in the evaluation of suprathreshold cough responses.

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role. Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles. The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation. Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), i.e., the rate of rise of IEMG activity. Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance. Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC during RC was longer (p < 0.01) than in controls. Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0. 01), especially during RC. Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -0.88, -0.86, and -0.85, respectively, p always < 0.01). The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease.

The assessment of cough threshold and intensity is important in respiratory medicine. We have developed a method for objectively and noninvasively assessing cough threshold and intensity of expiratory muscle efforts in response to inhalation of ultrasonically nebulized distilled water (UNDW). Thirty (83%) out of 36 volunteers studied coughed in response to UNDW inhalation. Cough threshold was taken as the lowest nebulizer output (mL x min(-1)) that induced cough in two challenges performed at a 30 min interval. At threshold level, repeatability of peak and slope of the integrated electromyographic (IEMG) activity of abdominal muscles was evaluated. Short- and long-term repeatability of cough threshold were evaluated in 15 subjects following a 3 h and a 6-9 month interval, respectively. Dose-response relationships between nebulizer outputs and IEMG-related variables were also investigated, as were the correlations between the latter and expiratory flow during voluntary coughing. The median (1st and 3rd quartile) cough threshold value was 0.89 (0.40 and 1.54) mL x min(-1). At threshold level, peak and slope of IEMG activity were highly reproducible. Cough threshold displayed a high degree of short- and long-term repeatability. Peak and slope of IEMG activity displayed a clear trend to increase (p<0.01) following inhalation of progressively higher UNDW outputs. Maximum flow during voluntary coughs of varying intensity correlated with the peak (p<0.05) and, more closely, with the slope (p<0.01) of abdominal IEMG activity. The assessment of cough threshold as well as the evaluation of the intensity of cough efforts by abdominal integrated electromyographic recordings may represent useful and reliable tools for cough research in humans.